Synthesis and antibiotic activity of a gramicidin S analogue containing bicyclic β-turn dipeptides

Sato, Kazuki; Nagai, Ukon

doi:10.1039/p19860001231

Cited by 78 publications

(28 citation statements)

References 2 publications

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“…Although it is stable to neat trifluoroacetic acid (TFA) at room had the same antibacterial activity as the original. 44 X-ray crystallography on a derivative shows a contemperature for 2 h and to hydrofluoric acid at 0ЊC for 1 h, 48 prolonged treatment of a derivative of formation with c 2 and f 3 values of 0161Њ and 069Њ, respectively. 41 In our conformational analysis of the 111 with TFA causes epimerization at the angular position to give 112, 46 which is also quite conacetyl and N-methylamide capped derivative, we found several structures with similar conformations strained, with torsions in the range 030Њ to /55Њ and distances in the range 3.5-7.8 Å .…”

Section: Torsionally Constrained Mimeticsmentioning

confidence: 99%

Conformational analysis of dipeptide mimetics

1997

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A compendium of compounds designed as dipeptide mimetics was collected from the literature. Conformational space available to these molecules was evaluated to obtain distance and torsion angle parameters to aid in selection of mimetics for specific target peptides or to explore diversity strategies. Conformations were searched using the RandomSearch algorithm in SYBYL. Data were collected for conformations of each molecule falling within 5 kcal/mol of the minimum. The distance between capping groups on the N‐ and C‐termini of the molecules was measured as well as the pseudotorsion angle about a virtual bond between these two points. Molecules are classified based on the torsion angle space occupied and range of distances spanned by the resulting conformations. A large percentage of the dipeptide mimetics studied here have redundant conformational properties. The distribution of distances for all molecules covers an overall range of 3–15 Å, the majority falling between 5–8 Å. The angles for the majority of the molecules cover a wide range of torsional space with essentially no gaps in the values they can occupy, although these molecules can be subdivided by the average distance spanned by the allowed conformations. A smaller group of molecules have torsion angles that are restricted to a range of ±60° about the cis position (0°). Representative examples of each group are shown. We conclude that despite the significant effort to devise unique molecular structures as dipeptide mimetics, there is a need for more conformationally restricted compounds to mimic specific peptide conformations, and to complement molecular diversity strategies. © 1997 John Wiley & Sons, Inc. Biopoly 43: 191–217, 1997

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Section: Torsionally Constrained Mimeticsmentioning

confidence: 99%

Conformational analysis of dipeptide mimetics

1997

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“…The d-Phe-Pro sequence of GS has been replaced by bicyclic thioindolizine derivatives [9,10] as well as the structurally related 5,6-fused azabicycloalkane [11] and indolizines. [12,13] In a related approach, several sugar amino acids (SAA) have been incorporated and their structural and biological properties studied.…”

Section: Introductionmentioning

confidence: 99%

Gramicidin S Derivatives Containing cis‐ and trans‐Morpholine Amino Acids (MAAs) as Turn Mimetics

Kapoerchan¹,

Spalburg²,

Neeling³

et al. 2010

Chemistry A European J

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The cyclic decapeptide gramicidin S (GS) was used as a model for the evaluation of four turn mimetics. For this purpose, one of the D‐Phe‐Pro two‐residue turn motifs in the rigid cyclic β‐hairpin structure of GS was replaced with morpholine amino acids (MAA 2–5), differing in stereochemistry and length of the side‐chain. The conformational properties of the thus obtained GS analogues (6–9) was assessed by using NMR spectroscopy and X‐ray crystallography, and correlated with their biological properties (antimicrobial and hemolytic activity). We show that compound 8, containing the dipeptide isostere trans‐MAA 4, has an apparent high structural resemblance with GS and that its antibacterial activity against a panel of Gram positive and ‐negative bacterial strains is better than the derivatives 6, 7 and 9.

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“…Thus these compounds have become interesting as potential drugs and indeed incorporation of some dipeptide mimetics into peptide sequences has given compounds with highly constrained geometries and useful biological activity. The external turn mimetic BTD, 1, prepared by Nagai 4-6 was an early example of such a compound and it was used successfully to replace the D-Phe-Pro dipeptide sequence in gramicidin S; 5 to prepare biologically active mimetics of enkephalin and luteinising hormone releasing factor (LRF); 6 and to replace residues 19 and 20 or 33 and 34 of ha CGRP , thus modelling the bioactive structure of the natural vasodilator peptide. 7 During our work on the synthesis of the bridged b-lactam 2, 8 we developed 9 a facile one-step synthesis of a series of bicyclic compounds 5 by the method summarised in Scheme 1.…”

Section: Introductionmentioning

confidence: 99%