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Full-Text Articles in Chemistry
Beyond Cell Penetrating Peptides: Designed Molecular Transporters, P. A. Wender, Christina B. Cooley, E. I. Geihe
Beyond Cell Penetrating Peptides: Designed Molecular Transporters, P. A. Wender, Christina B. Cooley, E. I. Geihe
Christina B Cooley
Inspired originally by peptides that traverse biological barriers, research on molecular transporters has since identified the key structural requirements that govern cellular entry, leading to new, significantly more effective and more readily available agents. These new drug delivery systems enable or enhance cellular and tissue uptake, can be targeted and provide numerous additional advantages of significance in imaging, diagnostics and therapy.
Inhibition Of Apobec3g Activity Impedes Double-Stranded Dna Repair, Ponnandy Prabhu, Shivender Shandilya, Elena Britan-Rosich, Adi Nagler, Celia Schiffer, Moshe Kotler
Inhibition Of Apobec3g Activity Impedes Double-Stranded Dna Repair, Ponnandy Prabhu, Shivender Shandilya, Elena Britan-Rosich, Adi Nagler, Celia Schiffer, Moshe Kotler
Celia A. Schiffer
The cellular cytidine deaminase APOBEC3G (A3G) was first described as an anti-HIV-1 restriction factor, acting by directly deaminating reverse transcripts of the viral genome. HIV-1 Vif neutralizes the activity of A3G, primarily by mediating degradation of A3G to establish effective infection in host target cells. Lymphoma cells, which express high amounts of A3G, can restrict Vif-deficient HIV-1. Interestingly, these cells are more stable in the face of treatments that result in double-stranded DNA damage, such as ionizing radiation and chemotherapies. Previously, we showed that the Vif-derived peptide (Vif25-39) efficiently inhibits A3G deamination, and increases the sensitivity of lymphoma cells to …
Nanomolar Binding Of Peptides Containing Noncanonical Amino Acids By A Synthetic Receptor, Leigh Logsdon, Christopher Schardon, Vijayakumar Ramalingam, Sharon Kwee, Adam Urbach
Nanomolar Binding Of Peptides Containing Noncanonical Amino Acids By A Synthetic Receptor, Leigh Logsdon, Christopher Schardon, Vijayakumar Ramalingam, Sharon Kwee, Adam Urbach
Adam R Urbach
This paper describes the molecular recognition of phenylalanine derivatives and their peptides by the synthetic receptor cucurbit[7]uril (Q7). The 4-tert-butyl and 4-aminomethyl derivatives of phenylalanine (tBuPhe and AMPhe) were identified from a screen to have 20–30-fold higher affinity than phenylalanine for Q7. Placement of these residues at the N-terminus of model tripeptides (X-Gly-Gly), resulted in no change in affinity for tBuPhe-Gly-Gly, but a remarkable 500-fold increase in affinity for AMPhe-Gly-Gly, which bound to Q7 with an equilibrium dissociation constant (Kd) value of 0.95 nM in neutral phosphate buffer. Structure–activity studies revealed that three functional groups work in a positively cooperative …
Dna Complexes: Durable Binders, Adam Urbach
Dna Complexes: Durable Binders, Adam Urbach
Adam R Urbach
The ability to program molecules to bind to specific sequences of DNA with high fidelity and stability is an important goal of chemical biology. Such molecules can compete with transcription-factor proteins and thus modulate the transcription of genes. They are therefore promising for both elucidating the complex regulation of mammalian gene expression, and developing pharmaceuticals and medical diagnostics targeted to genetic abberations. Writing in Nature Chemistry, Brent Iverson and co-workers have now described the excellent sequence specificity and unusual binding kinetics of a stable DNA–ligand complex, which exhibits a half-life of 16 days.
Sequence-Specific, Nanomolar Peptide Binding Via Cucurbit[8]Uril-Induced Folding And Inclusion Of Neighboring Side Chains, Lauren C. Smith, David G. Leach, Brittney E. Blaylock, Omar A. Ali, Adam R. Urbach
Sequence-Specific, Nanomolar Peptide Binding Via Cucurbit[8]Uril-Induced Folding And Inclusion Of Neighboring Side Chains, Lauren C. Smith, David G. Leach, Brittney E. Blaylock, Omar A. Ali, Adam R. Urbach
Adam R Urbach
This paper describes the molecular recognition of the tripeptide Tyr-Leu-Ala by the synthetic receptor cucurbit[8]uril (Q8) in aqueous buffer with nanomolar affinity and exceptional specificity. This combination of characteristics, which also applies to antibodies, is desirable for applications in biochemistry and biotechnology but has eluded supramolecular chemists for decades. Building on prior knowledge that Q8 binds to peptides with N-terminal aromatic residues, a library screen of 105 peptides was designed to test the effects of residues adjacent to N-terminal Trp, Phe, or Tyr. The screen used tetramethylbenzobis(imidazolium) (MBBI) as a fluorescent indicator and resulted in the unexpected discovery that MBBI …
Multivalent Recognition Of Peptides By Modular Self-Assembled Receptors, Joseph Reczek, Aimee Kennedy, Brian Halbert, Adam Urbach
Multivalent Recognition Of Peptides By Modular Self-Assembled Receptors, Joseph Reczek, Aimee Kennedy, Brian Halbert, Adam Urbach
Adam R Urbach
Developing nontraditional approaches to the synthesis and characterization of multivalent compounds is critical to our efforts to study and interface with biological systems and to build new noncovalent materials. This paper demonstrates a biomimetic approach to the construction of discrete, modular, multivalent receptors via molecular self-assembly in aqueous solution. Scaffolds presenting 1−3 viologen groups recruit a respective 1−3 copies of the synthetic host, cucurbit[8]uril, in a noncooperative manner and with a consistent equilibrium association constant (Ka) value of 2 × 106 M−1 per binding site. The assembled mono-, di-, and trivalent receptors bind to their cognate target peptides containing 1−3 …
Sequence-Specific Inhibition Of A Nonspecific Protease, Leigh Logsdon, Adam Urbach
Sequence-Specific Inhibition Of A Nonspecific Protease, Leigh Logsdon, Adam Urbach
Adam R Urbach
A nonspecific exopeptidase, aminopeptidase N (APN), is inhibited sequence-specifically by a synthetic host, cucurbit[7]uril (Q7), which binds with high affinity and specificity to N-terminal phenylalanine (Phe) and 4-(aminomethyl)phenylalanine (AMPhe) and prevents their removal from the peptide. Liquid chromatography experiments demonstrated that in the presence of excess Q7, APN quantitatively converts the pentapeptides Thr-Gly-Ala-X-Met into the dipeptides X-Met (X = Phe, AMPhe). The resulting Q7-bound products are completely stable to proteolytic digestion for at least 24 h. Structure–activity studies revealed a direct correlation between the extent of protection of an N-terminal amino acid and its affinity for Q7. Therefore, Q7 provides …
[60]Fullerene Amino Acids And Related Derivatives, Glenn A. Burley, Paul A. Keller, Stephen G. Pyne
[60]Fullerene Amino Acids And Related Derivatives, Glenn A. Burley, Paul A. Keller, Stephen G. Pyne
Paul Keller
This paper is a review of the literature concerning the preparation of [60]fullerene amino acid and peptide derivatives. The structure and applications of these derivatives to the biological and material sciences is also presented.