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Protein Structure Similarity Clustering: Dynamic Treatment Of Pdb Structures Facilitates Clustering, Bradley D. Charette, Richard G. Macdonald, Stefan Wetzel, David B. Berkowitz, Herbert Waldmann
Protein Structure Similarity Clustering: Dynamic Treatment Of Pdb Structures Facilitates Clustering, Bradley D. Charette, Richard G. Macdonald, Stefan Wetzel, David B. Berkowitz, Herbert Waldmann
David Berkowitz Publications
Protein structure similarity clustering (PSSC) [1]– [3] is one of a number of potential guiding principles [4], [5] that have been introduced to focus combinatorial-library design/ protein targeting. PSSC clusters protein targets with similar ligand-binding cores in which little sequence or functional similarity is evident. Lead compounds for one member of the cluster then provide novel starting points in chemical space for ligand development for other members of the PSSC. We describe herein a new clustering procedure that lends itself to ligand docking, molecular dynamics (MD), and the vector-alignment-search-tool (VAST) [6] algorithm. This MD-assisted approach offers an alternative to the …
Α-Vinylic Amino Acids: Occurrence, Asymmetric Synthesis, And Biochemical Mechanisms, David B. Berkowitz, Bradley D. Charette, Kannan Karukurichi, Jill M. Mcfadden
Α-Vinylic Amino Acids: Occurrence, Asymmetric Synthesis, And Biochemical Mechanisms, David B. Berkowitz, Bradley D. Charette, Kannan Karukurichi, Jill M. Mcfadden
David Berkowitz Publications
This report presents an overview of the family of naturally occurring “vinylic” amino acids, namely those that feature a C–C double bond directly attached to the α-carbon, along the side chain. Strategies that have been brought to bear on the stereo-controlled synthesis of these olefinic amino acids are surveyed. The mechanistic diversity by which such “vinylic triggers” can be actuated in a PLP (pyridoxal phosphate) enzyme active site is then highlighted by discussion of vinylglycine (VG), its substituted congeners, particularly AVG [4E-(2′-aminoethoxy)vinylglycine], and a naturally occurring VG-progenitor, SMM [(S)-methylmethionine].
A Formal [3,3]-Sigmatropic Rearrangement Route To Quaternary Α-Vinyl Amino Acids: Use Of Allylic N-Pmp Trifluoroacetimidates, David B. Berkowitz, Bin Wu, Huijie Li
A Formal [3,3]-Sigmatropic Rearrangement Route To Quaternary Α-Vinyl Amino Acids: Use Of Allylic N-Pmp Trifluoroacetimidates, David B. Berkowitz, Bin Wu, Huijie Li
David Berkowitz Publications
Pd(II)-mediated rearrangement of allylic N-PMP (p-methoxyphenyl) trifluoroacetimidates provides the first formal sigmatropic route to quaternary, α-vinylic amino acids, potential suicide substrates for PLP-enzymes. The amino acid side chains enter via transition metal-mediated C-C bond constructions, including (i) Cu(I)-mediated conjugate addition (Ala); (ii) Pd(0)/AsPh3-mediated Stille coupling (Allyl-Gly, Phe, DOPA, m-Tyr) and (iii) Pd(0)/Pt-Bu3-mediated Negishi coupling (Leu). In the synthesis of the DOPA decarboxylase inactivator, α-vinyl-m-tyrosine, the new N-PMP trifluoroacetimidate rearranges much more efficiently than the corresponding trichloroacetimidate.