3196-73-4Relevant articles and documents
The design of α/β-peptides: Study on three-residue turn motifs and the influence of achiral glycine on helix and turn
Sharma, Gangavaram V. M.,Chandramouli, Nagula,Basha, Shaik Jeelani,Nagendar, Pendem,Ramakrishna, Kallaganti V. S.,Sarma, Akella V. S.
, p. 84 - 97 (2011)
Novel three-residue helix-turn secondary structures, nucleated by a helix at the N terminus, were generated in peptides that have 'β-Caa-L-Ala-L-Ala, ' 'β-Caa-L-Ala-γ-Caa,' and 'β-Caa-L-Ala-γ-Caa' (in which β-Caa is C-linked carbo-β-amino acid, γ-Caa is C-linked carbo-γ-amino acid, and γ-Caa is C-linked carbo-γ-amino acid) at the C terminus. These turn structures are stabilized by 12-, 14-, and 15-membered (mr) hydrogen bonding between NH(i)/CO(i+2) (i+2 is the last residue in the peptide) along with a 7-mr hydrogen bond between CO(i)/NH(i+2). In addition, a series of α/β-peptides were designed and synthesized with alternating glycine (Gly) and (S)-β-Caa to study the influence of an achiral α-residue on the helix and helix-turn structures. In contrast to previous results, the three 'β-α-β' residues at the C terminus (α-residue being Gly) are stabilized by only a 13-mr forward hydrogen bond, which resembles an α-turn. Extensive NMR spectroscopic and molecular dynamics (MD) studies were performed to support these observations. The influence of chirality and side chain is also discussed. A turn for the better: α/β-Peptides with novel turns (12/7-, 14/7-, and 15/7-) at the C terminus were prepared. Similarly, the design with glycine gave an opportunity to study the influence of achiral α-residues on helix formation and stability. This study also resulted in a new 13-membered 'turn' in the forward direction, which resembles the α-turn (see picture). Copyright
Three-residue turn in β-peptides nucleated by a 12/10 helix
Sharma, Gangavaram V. M.,Yadav, Thota Anupama,Marumudi, Kanakaraju,Thodupunuri, Prashanth,Reddy, Pothula Purushotham,Kunwar, Ajit C.
, p. 3153 - 3162 (2014)
A new three-residue turn in β peptides nucleated by a 12/10-mixed helix is presented. In this design, β peptides were derived from the 1:1 alternation of C-linked carbo-β-amino acid ester [BocNH-(R)-β-Caa(r)-OMe] (Boc = tert-butyloxycarbonyl), which consisted of a D-ribo furanoside side chain, and β-hGly residues. The hexapeptide with (R)-β-Caa(r) at the N terminus showed the 'turn' stabilized by a 14-membered NH(4)...CO(6) hydrogen bond at the C terminus nucleated by a robust 12/10-mixed helix, thus providing a 'helix-turn' (HT) motif. The turn and the helix were additionally stabilized by intraresidue electrostatic interaction between the furan oxygen in the carbohydrate side chain and NH in the backbone. However, the hexapeptide with a β-hGly residue at the N terminus demonstrated the presence of a 10/12 helix through its entire length, which again showed the intraresidue interaction between NH and furan oxygen. The intraresidue NH...O-Me electrostatic interactions observed in the monomer, however, were absent in the peptides.
Synthesis of Nω,Νω–di-Boc-3-guanidylpropanal - An Important Reagent for Synthesis of Aza-Arg Precursors
Mastitski, Anton,Troska, Alla,J?rv, Jaak
, p. 472 - 478 (2021/09/18)
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Structure-Based Design and Development of Chemical Probes Targeting Putative MOR-CCR5 Heterodimers to Inhibit Opioid Exacerbated HIV-1 Infectivity
Huang, Boshi,Wang, Huiqun,Zheng, Yi,Li, Mengchu,Kang, Guifeng,Barreto-De-Souza, Victor,Nassehi, Nima,Knapp, Pamela E.,Selley, Dana E.,Hauser, Kurt F.,Zhang, Yan
, p. 7702 - 7723 (2021/06/28)
Crystal structures of ligand-bound G-protein-coupled receptors provide tangible templates for rationally designing molecular probes. Herein, we report the structure-based design, chemical synthesis, and biological investigations of bivalent ligands targeting putative mu opioid receptor C-C motif chemokine ligand 5 (MOR-CCR5) heterodimers. The bivalent ligand VZMC013 possessed nanomolar level binding affinities for both the MOR and CCR5, inhibited CCL5-stimulated calcium mobilization, and remarkably improved anti-HIV-1BaL activity over previously reported bivalent ligands. VZMC013 inhibited viral infection in TZM-bl cells coexpressing CCR5 and MOR to a greater degree than cells expressing CCR5 alone. Furthermore, VZMC013 blocked human immunodeficiency virus (HIV)-1 entry in peripheral blood mononuclear cells (PBMC) cells in a concentration-dependent manner and inhibited opioid-accelerated HIV-1 entry more effectively in phytohemagglutinin-stimulated PBMC cells than in the absence of opioids. A three-dimensional molecular model of VZMC013 binding to the MOR-CCR5 heterodimer complex is constructed to elucidate its mechanism of action. VZMC013 is a potent chemical probe targeting MOR-CCR5 heterodimers and may serve as a pharmacological agent to inhibit opioid-exacerbated HIV-1 entry.
Oxidative damage of proline residues by nitrate radicals (NO3): A kinetic and product study
Nathanael, Joses G.,Nuske, Madison R.,Richter, Annika,White, Jonathan M.,Wille, Uta
supporting information, p. 6949 - 6957 (2020/10/02)
Tertiary amides, such as in N-acylated proline or N-methyl glycine residues, react rapidly with nitrate radicals (NO3) with absolute rate coefficients in the range of 4-7 × 108 M-1 s-1 in acetonitrile. The major pathway proceeds through oxidative electron transfer (ET) at nitrogen, whereas hydrogen abstraction is only a minor contributor under these conditions. However, steric hindrance at the amide, for example by alkyl side chains at the α-carbon, lowers the rate coefficient by up to 75%, indicating that NO3-induced oxidation of amide bonds proceeds through initial formation of a charge transfer complex. Furthermore, the rate of oxidative damage of proline and N-methyl glycine is significantly influenced by its position in a peptide. Thus, neighbouring peptide bonds, particularly in the N-direction, reduce the electron density at the tertiary amide, which slows down the rate of ET by up to one order of magnitude. The results from these model studies suggest that the susceptibility of proline residues in peptides to radical-induced oxidative damage should be considerably reduced, compared with the single amino acid.