Influence of glucose-templated proline mimetics on the β-turn conformation of the peptide fragment Ac-Leu-d-Phe-Pro-Val-NMe2 found in Gramicidin S

The synthesis of tetrapeptide-based β-turn mimetics containing spirocyclic glucose-templated 3-hydroxyproline hybrids Glc3′(S)-5′(R)(CH2OH)HypH and Glc3′(S)-5′(S)(CH2OH)HypH as proline mimetics is presented. NMR-based conformational analysis of Ac-Leu-d-Phe-[Glc3′(S)-5′(R)(CH2OH)HypH]-Val-NMe2 and Ac-Leu-d-Phe-[Glc3′(S)-5′(S)(CH2OH)HypH]-Val-NMe2 demonstrates the presence of β-turn conformations. Different turn structures were observed by changing the stereochemistry at 5′-position of Glc3′(S)-5′(R)(CH2OH)HypH. The major prolyl amide cis isomer of glucose-protected tetrapeptide Ac-Leu-d-Phe-[Glc(MOM)43′(S)-5′(R)(CH2OMOM)HypH]-Val-NMe211 and glucose unprotected Ac-Leu-d-Phe-[Glc3′(S)-5′(R)(CH2OH)HypH]-Val-NMe213 forms a type VI β-turn conformation. In contrast, the major prolyl amide trans rotamer of tetrapeptide Ac-Leu-d-Phe-[Glc(MOM)43′(S)-5′(S)(CH2OMOM)HypH]-Val-NMe212 conserves a similar β-turn conformation as the Gramicidin S-based peptide fragment Ac-Leu-d-Phe-Pro-Val-NMe216.

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