Other Cell and Developmental Biology Commons^™

Developing A Protocol For Non-Cellular Transplantation Of Donor Mitochondria Into Recipient Cells, Andrew Parton

Honors Theses

Tumor innervation has emerged as a critical feature of cancer progression, with increased nerve density correlating with enhanced aggressiveness, metastatic dissemination, and poor clinical outcome. However, the functional contribution of neurons to tumor biology remains incompletely defined. We recently identified the intercellular transfer of mitochondria from neurons to cancer cells as a mechanism that promotes tumor progression. We therefore hypothesized that disruption of this transfer could attenuate tumor aggressivity. To directly investigate this process, we developed an approach to isolate mitochondria from donor cells and transplant them into recipient cancer cells independently of canonical cell-cell interactions. Transferred mitochondria were tracked …

The Impact Of Glucose Exposure On Organic Cation Transporters (Oct) Function In A Corneal Epithelial Cell Line, David A. Garza

Theses & Dissertations

Organic cation transporters (OCT) facilitate the movement of neurochemicals and medications, contribute to the removal of cellular waste, and facilitate neuronal communication. Three subtypes of these high-capacity, low-affinity transporters (OCT1, OCT2, and OCT3) are differently expressed in peripheral tissues such as the liver, kidneys, as well as the central nervous system. OCTs are also expressed in ocular tissues. Chronic hyperglycemia is a complication commonly associated with diabetes that can lead to ocular diseases such as diabetic keratopathy, which affects the cornea. In this project, we expose immortalized human corneal epithelial cells (HCE-S) to various glucose concentrations to study their impact …

Optimizing Itpa R178c Assays Via Hplc, Jared J. Reisnouer, Wally D. Pines

2026 Symposium

Two of the major nucleotide bases in DNA and RNA (Adenine and Guanine) are derived from the purine Inosine Monophosphate (IMP). IMP may occasionally form the noncanonical nucleotide Inosine Triphosphate (ITP) within the cell and become incorporated into DNA during replication, leading to potentially lethal errors. To combat this, human cells produce the “housekeeping” enzyme Inosine Triphosphatase (ITPA) to revert ITP to IMP. A mutation of this protein that replaces the 178th amino acid Arginine with Cysteine (R178C) is associated with a fatal infantile encephalopathy. Previous assessments of enzyme-substrate binding and catalysis for ITPA variants have been run at a …

The Cytotoxicity And Anti-Inflammatory Properties Of 1’S-1’-Acetoxychavicol Acetate (Aca) On Oral Cells, Nur Umairah Atiqah Sabri, Nor Syazwani Muhammad Zahidan, Zulfahmi Said, Siti Noor Adnalizawati Adnan, Normaliza Ab Malik

Journal of Dentistry Indonesia

Objective: Mouthwash is widely used to maintain oral health by reducing the prevalence of pathogenic microbiomes. Nonetheless, chlorhexidine, a common active ingredient, is associated with side effects including teeth staining, mucosal peeling, mouth and tongue numbness. This has prompted interest in natural alternatives. This study aimed to identify the cytotoxicity and anti-inflammatory properties of 1’S-1’-acetoxychavicol acetate (ACA) isolated from Alpinia conchigera rhizome against human primary gingival fibroblast and keratinocyte (HPGF and HPGK). Methods: Cytotoxicity of ACA (1.57 mg/mL) against HPGF and HPGK was assessed using the MTT assay. Meanwhile, the anti-inflammatory property of ACA was analyzed based on …

Epidemiology, Presentation, And Diagnosis Of Type 2 Diabetes Mellitus In Children And Adolescents, Bisher Alsabbagh, Whard Alsabbagh

School of Integrative Biological & Chemical Sciences (Formerly Dept. of Biology)

The prevalence of type 2 diabetes mellitus (T2DM) in children and adolescents has increased substantially over recent decades, paralleling rising rates of pediatric obesity and metabolic risk. Youth-onset T2DM is characterized by significant insulin resistance accompanied by an inadequate compensatory insulin response, resulting in progressive hyperglycemia and early beta-cell dysfunction. Incidence varies widely among racial and ethnic groups, with the highest rates observed in non-Hispanic Black, Hispanic, Native American, Asian American, and Pacific Islander youth. Risk factors include obesity, family history, high-risk ethnicity, pubertal insulin resistance, prenatal metabolic exposures, and comorbid conditions such as polycystic ovary syndrome. Clinical presentation ranges …

The Differential Effects Of Camp Mobilizing Agents On Tgf-Β-Induced Extracellular Matrix In Human Lung-Derived Fibroblasts: Insights Into Therapeutic Targets For Lung Fibrosis, Sarah Orfanos, Brian T. Deeney, Gaoyuan Cao, Nikhil Karmacharya, Anjani Ravi, Cynthia J. Koziol-White, Qi Yang, Rennolds S. Ostrom, Reynold A. Panettieri Jr.

Pharmacy Faculty Articles and Research

Background

Injury-repair responses typically induce tissue or organ scarring. Generally, cAMP-mobilizing agents inhibit the activation of fibroblasts and deposition of extracellular matrix. Some but not all cAMP-mobilizing agents inhibit fibrosis. Evidence suggests that inhaled treprostinil, a prostacyclin (IP) analog, increases intracellular cAMP levels [cAMP]I, and slows the decline in pulmonary function in patients with idiopathic pulmonary fibrosis (IPF). However, the molecular mechanisms by which cAMP-mobilizing agents, including treprostinil, alter the expression of matrix proteins in human lung fibroblasts (HLF) remain unclear. Unlike other Gαs -coupled receptors, we posit that the antifibrotic properties of treprostinil are driven by cAMP-mobilizing-dependent and -independent …

The Impact Of Paternal Obesity On Placental Development And Function During Pregnancy, Delaney G. Wolfe, Delaney G. Wiolfe

Department of Nutrition Student Projects

Paternal obesity is a rising concern in conception and reproductive health, with increasing evidence suggesting its impact on pregnancy outcomes. While maternal obesity's effects on fetal development and placental function are well-documented, the role of paternal obesity remains less understood. The placenta, crucial for nutrient exchange and fetal development, can be disrupted by inflammation, oxidative stress, and epigenetic modifications, potentially leading to long-term health implications for both maternal and fetal health. Understanding the paternal influence on placental development is essential for improving pregnancy outcomes and offspring
health. This study aims to investigate the relationship between paternal obesity on placental function …

Comprehensive Sumo Proteomic Analyses Identify Hiv Latency-Associated Proteins In Microglia., Fergan Imbert, Dianne Langford

Rowan-Virtua School of Osteopathic Medicine Departmental Research

SUMOylation, the post-translational modification of proteins by small ubiquitin-like modifiers, plays a critical role in regulating various cellular processes, including innate immunity. This modification is essential for modulating immune responses and influencing signaling pathways that govern the activation and function of immune cells. Recent studies suggest that SUMOylation also contributes to the pathophysiology of central nervous system (CNS) viral infections, where it contributes to the host response and viral replication dynamics. Here, we explore the multifaceted role of SUMOylation in innate immune signaling and its implications for viral infections within the CNS. Notably, we present novel proteomic analyses aimed at …

Tdp43 Autoregulation Gives Rise To Dominant Negative Isoforms That Are Tightly Controlled By Transcriptional And Post-Translational Mechanisms, Megan M. Dykstra, Kaitlin Weskamp, Nicolás B. Gómez, Jacob Waksmacki, Elizabeth Tank, M. Rebecca Glineburg, Allison Snyder, Emile Pinarbasi, Michael Bekier, Xingli Li, Morgan R. Miller, Jen Bai, Shameena Shahzad, Neha Nedumaran, Clare Wieland, Corey Stewart, Sydney Willey, Nikolas Grotewold, Jonathon Mcbride, John J. Moran, Aditya V. Suryakumar, Michael Lucas, Peter M. Tessier, Michael Ward, Peter K. Todd, Sami J. Barmada

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

The nuclear RNA-binding protein TDP43 is integrally involved in the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Previous studies uncovered N-terminal TDP43 isoforms that are predominantly cytosolic in localization, prone to aggregation, and enriched in susceptible spinal motor neurons. In healthy cells, however, these shortened (s)TDP43 isoforms are difficult to detect in comparison to full-length (fl)TDP43, raising questions regarding their origin and selective regulation. Here, we show that sTDP43 is created as a by-product of TDP43 autoregulation and cleared by nonsense-mediated RNA decay (NMD). sTDP43-encoding transcripts that escape NMD are rapidly degraded post-translationally via the proteasome …

Effects Of Round-Up On The Environment, Sandra J. Marcu

Journal of Earth and Life Science

Many people around the world have used and still currently use Roundup but are unaware of the effects it has on the environment. Roundup is a spray on application weedkiller that is widely used around the world today both residentially and commercially. It enables its user to grow a garden or a field of crops with a no-tilling approach to eliminate weeds. It is a well-known and popular choice for killing weeds that has been around since the mid 1970’s (Oca, 2017). John Franz, a Monsanto scientist discovered that glyphosate (main ingredient in Roundup) was an herbicide or weedkiller, and …

Early Host Defense Against Virus Infections, Søren R. Paludan, Thomas Pradeu, Andreas Pichlmair, K. Brad Wray, Jacob Giehm Mikkelsen, David Olagnier, Trine H. Mogensen

Presidential Fellows Articles and Research

Early host defense eliminates many viruses before infections are established while clearing others so they remain subclinical or cause only mild disease. The field of immunology has been shaped by broad concepts, including the pattern recognition theory that currently dominates innate immunology. Focusing on early host responses to virus infections, we analyze the literature to build a working hypothesis for the principles that govern the early line of cellular antiviral defense. Aiming to ultimately arrive at a criteria-based theory with strong explanatory power, we propose that both controlling infection and limiting inflammation are key drivers for the early cellular antiviral …

Identifying The Roles Of Mir-17 In Ciliogenesis And Cell Cycle, Ashwaq Alanazi, Ayan K. Barui, Ashraf M. Mohieldin, Ankan Gupta, Ramani Ramachandran, Surya M. Nauli

Pharmacy Faculty Articles and Research

Emerging evidence suggests a significant contribution of primary cilia to cell division and proliferation. MicroRNAs, especially miR-17, contribute to cell cycle regulation and proliferation. Recent investigations have highlighted the dysregulated expression of miR-17 in various malignancies, underlining its potential role in cancer. However, the correlation between primary cilia and miR-17 has yet to be fully elucidated. The present study examines the presence of miR-17 in primary cilia. The miR-17 expression is studied in selected ciliary protein knockdown cells. Using in situ hybridization (ISH), we identified the subcellular localization of miR-17 in both cilium and cell body. We confirmed the importance …

An Exploration Of The Effectiveness Of Xanthorrhiza Simplicissima And Its Secondary Alkaloids As Antibiotics Against Staphylococcus Aureus With The Use Of Reserpine, Donald Bothe, Savita Chaurasia

Undergraduate Theses

Xanthorhiza simplicissima is a plant that is steeped in medical history. It has been used for hundreds of years by the Native Americans, and later by the Europeans, of Appalachia for its medicinal properties. One of the most useful medical applications of this plant are its antibiotic properties, as typified by its use as a tea that was consumed to treat mouth sores. These antibiotic properties can be attributed to some of its secondary alkaloids such as berberine, liriodenine, oxyacanthine, and magnoflorine. These compounds have been studied in other systems; however, oxyacanthine and magnoflorine have not been researched in tandem …

Methamphetamine-Induced Dna Double-Stranded Breaks: The Impact Of The Dopamine Transporter And Insights Into The Mechanisms Of Dna Damage In Mouse Neuro 2a Cells, Lizette Couto

Dissertations, Theses, and Capstone Projects

Methamphetamine (METH) abuse remains a global health concern, with emerging evidence highlighting its genotoxic potential. In the central nervous system METH enters dopaminergic cells primarily through the dopamine transporter (DAT), which controls the dynamics of dopamine (DA) neurotransmission by driving the reuptake of extracellular DA into the presynaptic neuronal cell. Additional effects of METH on the storage of DA in synaptic vesicles lead to the dysregulated cytosolic accumulation of DA. Previous studies have shown that after METH disrupts intracellular vesicular stores of DA, the excess DA in the cytosol is rapidly oxidized. This generates an abundance of reactive oxygen species …

The Pros Of Changing Trna Identity, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

The notion that errors in protein synthesis are universally harmful to the cell has been questioned by findings that suggest such mistakes may sometimes be beneficial. However, how often these beneficial mistakes arise from programmed changes in gene expression as opposed to reduced accuracy of the translation machinery is still unclear. A new study published in JBC shows that some bacteria have beneficially evolved the ability to mistranslate specific parts of the genetic code, a trait that allows improved antibiotic resistance.

Chemoattractant Distribution In Complex Geometry Impacts The Trajectory Of Clustered Cell Migration, Naghmeh Akhavan

Biology and Medicine Through Mathematics Conference

No abstract provided.

Understanding The Expression And Role Of Pros-1 In The Male Gonad Of C. Elegans, Jack Bozik

Undergraduate Theses

The gene pros-1 is a transcription factor that is highly expressed within neuronal sheath cells, glial cells, and excretory canal cells. pros-1 plays a role in cell determination of those cell types in the nematode C. elegans, which promotes organismal development. But the degree to which pros-1 presence is important is still not fully understood, because there are many genes involved in development that when mutated or damaged can result in unexpected phenotypes or even total loss of function to a certain developmental mechanism. What makes pros-1 valuable to research is that it is a functional homologue to a …

Characterizing Cellular Injury And Inflammation With Aldob-/-Mouse Model Of Mafld, Andy Rashid

All Master's Theses

Metabolic-associated fatty liver disease (MAFLD) affects 1 in 3 people in the US and is a healthcare burden on the order of billions of dollars. MAFLD is characterized by pathological lipid accumulation in the liver, excess production of triglycerides and cholesterol, and export of LDL particles that raise serum lipid levels. These metabolic perturbations can lead to the development of liver fibrosis, chronic inflammation, and insulin resistance. Diagnosing MAFLD prior to fibrosis is crucial for successful intervention and prevention of advanced liver disease and other metabolic complications. Fructose-1Phospahte (F1P) accumulation from fructose overconsumption can drive hepatic lipogenesis and MAFLD progression. …

Therapies For Mitochondrial Disorders, Kayli Sousa Smyth, Anne Mulvihill

SURE Journal: Science Undergraduate Research Experience Journal

Mitochondria are cytoplasmic, double-membrane organelles that synthesise adenosine triphosphate (ATP). Mitochondria contain their own genome, mitochondrial DNA (mtDNA), which is maternally inherited from the oocyte. Mitochondrial proteins are encoded by either nuclear DNA (nDNA) or mtDNA, and both code for proteins forming the mitochondrial oxidative phosphorylation (OXPHOS) complexes of the respiratory chain. These complexes form a chain that allows the passage of electrons down the electron transport chain (ETC) through a proton motive force, creating ATP from adenosine diphosphate (ADP). This study aims to explore current and prospective therapies for mitochondrial disorders (MTDS). MTDS are clinical syndromes coupled with abnormalities …

The Novel Role Of Dnmbp In Kidney Development, Brandy Walker

Dissertations and Theses (Open Access)

Congenital anomalies of the kidney and urinary tract (CAKUT) accounts for nearly one-fourth of all birth defects and more than 40% of pediatric end-stage renal disease, yet only 10-20% of CAKUT cases have a known monogenetic cause. Human kidneys are composed of up to a million epithelial tubules called nephrons. Disruption of nephron development is one of the many congenital anomalies that cause CAKUT, often resulting in chronic or end-stage renal disease which requires transplant. During nephron epithelialization, the formation of stable cadherin-mediated adhesion junctions is essential for maintaining cell-cell contacts. To understand the cell behaviors underlying abnormalities in renal …

Hyper Stable Variants Of Fgf-1-Fgf-2 Dimer, Madison Shields Mcclanahan

Chemistry & Biochemistry Undergraduate Honors Theses

Fibroblast Growth Factors (FGFs), including FGF-1 and FGF-2, are proteins that play a crucial role in cell proliferation, cell differentiation, cell migration, and tissue repair. FGF-1 and FGF-2 are useful in accelerating the healing process in the human body; however, these proteins are naturally thermally unstable, resulting in a relatively low half-life in vivo. 1,8 In efforts to improve the stability of this protein, FGF-1 and FGF-2 proteins are engineered by combining the amino acid sequences of the two proteins to form a heterodimer and obtain novel properties. These two FGF variants are chosen for their specific wound healing capabilities. …

Amphiphilic Cell-Penetrating Peptides Containing Natural And Unnatural Amino Acids As Drug Delivery Agents, David Salehi, Saghar Mozaffari, Khalid Zoghebi, Sandeep Lohan, Dindyal Mandal, Rakesh Tiwari, Keykavous Parang

Pharmacy Faculty Articles and Research

A series of cyclic peptides, [(DipR)(WR)₄], [(DipR)₂(WR)₃], [(DipR)₃(WR)₂], [(DipR)₄(WR)], and [DipR]₅, and their linear counterparts containing arginine (R) as positively charged residues and tryptophan (W) or diphenylalanine (Dip) as hydrophobic residues, were synthesized and evaluated for their molecular transporter efficiency. The in vitro cytotoxicity of the synthesized peptides was determined in human epithelial ovary adenocarcinoma cells (SK-OV-3), human lymphoblast peripheral blood cells (CCRF-CEM), human embryonic epithelial kidney healthy cells (HEK-293), human epithelial mammary gland adenocarcinoma cells (MDA-MB-468), pig epithelial kidney normal cells (LLC-PK1), and human epithelial …

Escherichia Coli Alanyl-Trna Synthetase Maintains Proofreading Activity And Translational Accuracy Under Oxidative Stress, Arundhati Kavoor, Paul Kelly, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Aminoacyl-tRNA synthetases (aaRSs) are enzymes that synthesize aminoacyl-tRNAs to facilitate translation of the genetic code. Quality control by aaRS proofreading and other mechanisms maintains translational accuracy, which promotes cellular viability. Systematic disruption of proofreading, as recently demonstrated for alanyl-tRNA synthetase (AlaRS), leads to dysregulation of the proteome and reduced viability. Recent studies showed that environmental challenges such as exposure to reactive oxygen species can also alter aaRS synthetic and proofreading functions, prompting us to investigate if oxidation might positively or negatively affect AlaRS activity. We found that while oxidation leads to modification of several residues in Escherichia coli AlaRS, unlike …

Analysis Of Hematocrit Levels In Walleye Sander Vitreus From Similar Waterbodies, Alyssa Hauser

Journal of Earth and Life Science

Walleye Sander vitreus are a popular fish among anglers and hold a prominent place in Minnesotan’s identity as their state fish. Because of this, multiple management practices are used to ensure the continued health of their populations within Minnesota waters. In this study, the process of analyzing hematocrit levels was used to determine if the analysis of hematological parameters could be a useful tool in detecting differences in population health. To evaluate this, blood samples were acquired from age-0 and age-1 fish from two similar lakes and run through a hematocrit centrifuge to separate platelets from plasma to read the …

Keratin 1 As A Cell-Surface Receptor In Cancer, Oluseye Ogunnigbagbe, Christopher G. Bunick, Kamaljit Kaur

Pharmacy Faculty Articles and Research

Keratins are fibrous proteins that take part in several important cellular functions, including the formation of intermediate filaments. In addition, keratins serve as epithelial cell markers, which has made their role in cancer progression, diagnosis, and treatment an important focus of research. Keratin 1 (K1) is a type II keratin whose structure is comprised of a coiled-coil central domain flanked by flexible, glycine-rich loops in the N- and C-termini. While the structure of cytoplasmic K1 is established, the structure of cell-surface K1 is not known. Several transformed cells, such as cancerous cells and cells that have undergone oxidative stress, display …

Physiological Roles Of Mammalian Transmembrane Adenylyl Cyclase Isoforms, Katrina F. Ostrom, Justin E. Lavigne, Tarsis F. Brust, Roland Seifert, Carmen Dessauer, Val J. Watts, Rennolds S. Ostrom

Pharmacy Faculty Articles and Research

Adenylyl cyclases (ACs) catalyze the conversion of ATP to the ubiquitous second messenger cAMP. Mammals possess nine isoforms of transmembrane ACs, dubbed AC1-9, that serve as major effector enzymes of G protein-coupled receptors. The transmembrane ACs display varying expression patterns across tissues, giving potential for them having a wide array of physiologic roles. Cells express multiple AC isoforms, implying that ACs have redundant functions. Furthermore, all transmembrane ACs are activated by Gα_s so it was long assumed that all ACs are activated by Gα_s-coupled GPCRs. AC isoforms partition to different microdomains of the plasma membrane and form …

Regulation Of Brain Primary Cilia Length By Mch Signaling: Evidence From Pharmacological, Genetic, Optogenetic, And Chemogenic Manipulations, Wedad Alhassen, Yuki Kobayashi, Jessica Su, Brianna Robbins, Henry Nguyen, Thant Myint, Micah Yu, Surya M. Nauli, Yumiko Saito, Amal Alachkar

Pharmacy Faculty Articles and Research

The melanin-concentrating hormone (MCH) system is involved in numerous functions, including energy homeostasis, food intake, sleep, stress, mood, aggression, reward, maternal behavior, social behavior, and cognition. In rodents, MCH acts on MCHR1, a G protein-coupled receptor, which is widely expressed in the brain and abundantly localized to neuronal primary cilia. Cilia act as cells’ antennas and play crucial roles in cell signaling to detect and transduce external stimuli to regulate cell differentiation and migration. Cilia are highly dynamic in terms of their length and morphology; however, it is not known if cilia length is causally regulated by MCH system activation …

A Comparison Of Calcium Aggregation And Ultracentrifugation Methods For The Preparation Of Rat Brain Microsomes For Drug Metabolism Studies, Barent N. Dubois, Farideh Amirrad, Reza Mehvar

Pharmacy Faculty Articles and Research

Preparation of brain microsomes by the calcium chloride aggregation method has been suggested as an alternative to the ultracentrifugation method. However, the effects of the calcium chloride concentration on the quality of the microsomal fractions are not known. Brain microsomes were prepared from the adult rat brains using the high-speed ultracentrifugation and low-speed calcium chloride (10–100 mM) aggregation methods (n = 5–6 per group). The microsomal protein yield (spectrometry), the cytochrome P450 reductase (CPR) activity (spectrometry), and the monooxygenase activities (UPLC-MS/MS) of CYP2D and CYP2E1 were determined in the obtained fractions. Increasing the concentrations of calcium chloride progressively increased …

Proteoglycan-4 Is An Essential Regulator Of Synovial Macrophage Polarization And Inflammatory Macrophage Joint Infiltration, Marwa Qadri, Gregory D. Jay, Ling X. Zhang, Tannin A. Schmidt, Jennifer Totonchy, Khaled A. Elsaid

Pharmacy Faculty Articles and Research

Background

Synovial macrophages perform a multitude of functions that include clearance of cell debris and foreign bodies, tissue immune surveillance, and resolution of inflammation. The functional diversity of macrophages is enabled by distinct subpopulations that express unique surface markers. Proteoglycan-4 (PRG4) is an important regulator of synovial hyperplasia and fibrotic remodeling, and the involvement of macrophages in PRG4’s synovial role is yet to be defined. Our objectives were to study the PRG4’s importance to macrophage homeostatic regulation in the synovium and infiltration of pro-inflammatory macrophages in acute synovitis and investigate whether macrophages mediated synovial fibrosis in Prg4 gene-trap (Prg4 …

Design And Application Of Hybrid Cyclic-Linear Peptide-Doxorubicin Conjugates As A Strategy To Overcome Doxorubicin Resistance And Toxicity, Saghar Mozaffari, David Salehi, Parvin Mahdipoor, Richard Beuttler, Rakesh Tiwari, Hamidreza Montazeri Aliabadi, Keykavous Parang

Pharmacy Faculty Articles and Research

Doxorubicin (Dox) is used for breast cancer, leukemia, and lymphoma treatment as an effective chemotherapeutic agent. However, Dox use is restricted due to inherent and acquired resistance and an 8-fold increase in the risk of potentially fatal cardiotoxicity. Hybrid cyclic-linear peptide [R5K]W7A and linear peptide R5KW7A were conjugated with Dox through a glutarate linker to afford [R5K]W7A-Dox and R5KW7A-Dox conjugates to generate Dox derivatives. Alternatively, [R5K]W7C was conjugated with Dox via a disulfide linker to generate [R5K]W7C–S–S-Dox conjugate, where S–S is a disulfide bond. Comparative antiproliferative assays between conjugates [R5K]W7A-Dox, [R5K]W7C–S–S-Dox, linear R5KW7A-Dox, the corresponding physical mixtures of the peptides, …