- Role of side-chain and chirality of the amino acids on the supramolecular assemblies of dipeptides
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The supramolecular self-association of alternating L/L and L/D amino acid-containing dipeptides, Boc-L-Ile-L-Phe-OMe (1), Boc-L-Ile-D-Phe-OMe (2), Boc-L-Ile-L-Phg-OMe (3, Phg = phenylglycine), and Boc-L-Ile-D-Phg-OMe (4) have been investigated. The presence of extra methylene (-CH2-) group on the side-chain of C-terminal Phe-of 1 causes a significant deviation of molecular arrangements from that of 3. While the molecules in 1 self-assemble to form a single helix-like architecture, the molecules in 3 self-associate around a water molecule to form a cylinder-like structure in the crystalline state. Alternatively, the observed supramolecular arrangements of 2 and 4 are similar, but deviate from that of 1 and 3, due to chirality difference. Peptides 2 and 4 exhibit a discontinued double helix-like structure in the crystalline state. While 1 and 3 self-associate to form helical ribbon-like and nano tube-like structures, respectively, both 2 and 4 form nano rod-like structures in solution.
- Dolai, Gobinda,Giri, Rajat Subhra,Mandal, Bhubaneswar,Roy, Sayanta
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Read Online
- Synthesis and anticancer activities of proline-containing cyclic peptides and their linear analogs and congeners
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A solution phase method was adopted for the synthesis of proline-containing cyclic pentapeptide 2 and total synthesis of naturally occurring cyclic heptapeptide Reniochalistatin B 3. For the synthesis of 3, both divergent and convergent strategies were used to improve the overall yield from 12 to 25%. Different N and C terminal modified linear analogs and congeners of 2 and 3 were synthesized. Both cyclic peptides 2 and 3 and their linear analogs/congeners were evaluated for anti-cancer activity against HeLa cell line, among which pentapeptide 2 h and hexapeptide 3n with N-terminal protected hexafluoroisopropyl carbamates (HFIPC) interestingly showed higher cytotoxicity with an IC50 of 2.73 and 4.3 μM, respectively compared to their Boc-protected analogs 2a (IC50 20 μM) and 3c (IC50 38.51 μM) and cyclic peptides 2 (>100 μM) and 3 (47 μM). These results were further validated by biological experiments such as colony formation and wound healing assays.
- Ghosh, Keshab Ch,Duttagupta, Indranil,Bose, Chandra,Banerjee, Priyanjalee,Gayen, Anuran Kumar,Sinha, Surajit
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supporting information
p. 221 - 236
(2019/01/19)
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- Pd-Catalyzed Site-Selective C(sp2)-H Olefination and Alkynylation of Phenylalanine Residues in Peptides
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Pd-catalyzed site-selective C(sp2)-H olefination and alkynylation of phenylalanine residues in peptides are described. The amino acids within the peptides are used as native bidentate directing groups to facilitate C-H functionalization. This p
- Zheng, Yong,Song, Weibin
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supporting information
(2019/05/08)
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- Cyrene as a bio-based solvent for HATU mediated amide coupling
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Amide bonds are one of the underpinning linkages in all living systems and are fundamental within drug discovery. Current methods towards their synthesis frequently rely on the use of dipolar aprotic solvents; however, due to increasingly stringent regula
- Wilson, Kirsty L.,Murray, Jane,Jamieson, Craig,Watson, Allan J. B.
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supporting information
p. 2851 - 2854
(2018/05/03)
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- Pd-catalyzed intramolecular C(sp2)-H amination of phenylalanine moieties in dipeptides: Synthesis of indoline-2-carboxylate-containing dipeptides
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A palladium-catalyzed intramolecular C(sp2)-H amination of phenylalanine moieties in dipeptides is described. By this protocol, a series of indoline-2-carboxylate-containing dipeptides were synthesized from dipeptides. The N-protected amino aci
- Zheng, Yong,Song, Weibin,Zhu, Yefu,Wei, Bole,Xuan, Lijiang
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supporting information
p. 2402 - 2405
(2018/04/12)
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- Diketo acids and their amino acid/dipeptidic analogues as promising scaffolds for the development of bacterial methionine aminopeptidase inhibitors
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Using diketoesters as the template, various derivatives were designed and the selected compounds were synthesized as bacterial methionine aminopeptidase (MetAP) inhibitors. The results of in vitro antibacterial screening revealed fifteen compounds (1a-c,
- Masood, Mir Mohammad,Pillalamarri, Vijay K.,Irfan, Mohammad,Aneja, Babita,Jairajpuri, Mohamad Aman,Zafaryab,Rizvi, M. Moshahid A.,Yadava, Umesh,Addlagatta, Anthony,Abid, Mohammad
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p. 34173 - 34183
(2015/04/27)
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- Synthesis, characterization and antimicrobial studies on some newer imidazole analogs
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A novel series of 3,5-diiodo-4-(2-methyl-1H-imidazol-5-yl)benzoic acid analogs of amino acids, dipeptides and tripeptides was synthesized by using dicyclohexylcarbodiimide and diisopropylcarbodiimide (DCC/DIPC) as coupling agents and triethylamine (TEA) as base. Structures of all the newly synthesized compounds were confirmed by elemental analysis and IR, 1H NMR, 13C NMR and mass spectral data. Imidazolopeptides were investigated for their antimicrobial activity and some of newly synthesized compounds 2c, 2d, 2h and their hydrolyzed analogs 3b, 3d exhibited potent bioactivity against pathogenic fungi Candida albicans and dermatophytes Trichophyton mentagrophytes and Microsporum audouinii with MIC values of 12.5-6 μg/ml, as compared to the reference drug - griseofulvin. In addition, moderate activity against gram negative bacteria Pseudomonas aeruginosa and Klebsiella pneumoniae was also observed for synthesized imidazolopeptides. Oesterreichische Apotheker-Verlagsgesellschaft m. b. H.
- Dahiya, Rajiv
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p. 217 - 239
(2008/12/22)
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- Synthesis and activity of HIV protease inhibitors
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We report here the synthesis and activity of HIV protease inhibitors. In the first stage hydrophobic compounds incorporating a 'carba' bond surrogate or a beta-homologated residue were synthesized. Secondly, we synthesized cyclic compounds in which we incorporated 2-quinoline carboxylic acid in the P3 position and the amino-hydroxyindane moiety in the P'3. The last part of this work was dedicated to a structure/activity study of a peptide substrate. These modifications allowed us to work up the synthesis of new pseudopeptide bonds: amino-amide and hydroxy-amide. Compounds with activity in the micromolar range were actually a starting point for the synthesis of new protease inhibitors.
- Garrouste, Patrick,Pawlowski, Macek,Tonnaire, Thierry,Sicsic, Sames,Dumy, Pascal,De Rosny, Eve,Reboud-Ravaux, Michele,Fulcrand, Pierre,Martinez, Jean
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p. 423 - 436
(2007/10/03)
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- New hydroxyethylamine HIV protease inhibitors that suppress viral replication
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The synthesis of analogues of AcSerLeuAsn[Phe-HEA-Pro]IleValOMe (1, JG- 365; where HEA stands for the hydroxyethylamine unit 2), a tight-binding inhibitor of HIVP, are reported. Systematic modification of the P3 and P3' regions of the inhibitors has led to smaller HIVP inhibitors that inhibit viral replication in HIV-infected and SIV-infected cell cultures. Six aliphatic and/or aromatic derivatives were prepared by replacing residues in the P3 regions of BocLeuAsn[Phe-HEA-Pro]IleValOMe. Aromatic side chains at P3 gave better inhibitors than aliphatic side chains. The better inhibitors in this series contained a β-naphthylalanine or a biphenyl unit at P3. A second series of HIVP inhibitors were obtained by converting the P3 group into acyl groups. CbzAsn[Phe-HEA-Pro]IlePheOMe and Qua-Asn-[Phe-HEA-Pro]-Ile- Phe-OMe (where Qua = quinolin-2-ylcarbonyl) are potent HIVP inhibitors with K(i) values equal to 1.0 and 0.1 nM, respectively. The inhibition constants were determined by using the continuous fluorometric assay developed by Toth and Marshall. The activities of the protease inhibitors for inhibition of SIV replication were determined in vitro using CEMx174 cells. Inhibition of HIV infection was determined essentially as reported by Pauwels and co-workers. The anti-HIV assay was carried out in culture using CEM cells (a CD4+ lymphocyte line) infected with virus strain HTLV-III(b) with a multiplicity of infection of 0.1. Several analogues inhibited the cytopathic effect at concentrations of 0.1-0.8 μg/mL. These results establish that good inhibitors of HIV protease that inhibit viral replication in infected lymphocytes in in vitro cell assays can be obtained from JG-365 when the AcSerLeu unit is replaced by aromatic acyl derivatives.
- Rich,Vara Prasad,Sun,Green,Mueller,Houseman,MacKenzie,Malkovsky
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p. 3803 - 3812
(2007/10/02)
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- Renin inhibitors containing ψ[CH2O]pseudopeptide inserts
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Renin inhibitors 2-4 with the D-Lys renin inhibitory peptide (RIP) sequence, but containing Leuψ[CH2O]Ala (2), Leuψ[CH2O]Val (3), and Leuψ[CH2O]Leu (4) at the P1-P1' site, were of a comparable potency
- TenBrink,Pals,Harris,Johnson
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p. 671 - 677
(2007/10/02)
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