Influence of glucose-templated proline mimetics on the beta-turn conformation of the peptide fragment Ac-Leu-D-Phe-Pro-Val-NMe2 found in Gramicidin S.
The synthesis of tetrapeptide-based beta-turn mimetics containing spirocyclic glucose-templated 3-hydroxyproline hybrids Glc3'(S)-5'(R)(CH(2)OH)HypH and Glc3'(S)-5'(S)(CH(2)OH)HypH as proline mimetics is presented. NMR-based conformational analysis of Ac-Leu-D-Phe-[Glc3'(S)-5'(R)(CH(2)OH)HypH]-Val-NMe(2) and Ac-Leu-D-Phe-[Glc3'(S)-5'(S)(CH(2)OH)HypH]-Val-NMe(2) demonstrates the presence of beta-turn conformations. Different turn structures were observed by changing the stereochemistry at 5'-position of Glc3'(S)-5'(R)(CH(2)OH)HypH. The major prolyl amide cis isomer of glucose-protected tetrapeptide Ac-Leu-D-Phe-[Glc(MOM)(4)3'(S)-5'(R)(CH(2)OMOM)HypH]-Val-NMe(2)11 and glucose unprotected Ac-Leu-D-Phe-[Glc3'(S)-5'(R)(CH(2)OH)HypH]-Val-NMe(2)13 forms a type VI beta-turn conformation. In contrast, the major prolyl amide trans rotamer of tetrapeptide Ac-Leu-D-Phe-[Glc(MOM)(4)3'(S)-5'(S)(CH(2)OMOM)HypH]-Val-NMe(2)12 conserves a similar beta-turn conformation as the Gramicidin S-based peptide fragment Ac-Leu-D-Phe-Pro-Val-NMe(2)16.
Zhang
Kaidong
K
Department of Chemistry, University of Manitoba-Winnipeg, Manitoba, Canada.
Schweizer
Frank
F
D000595:Amino Acid Sequence; D032701:Biomimetics; D005947:Glucose / Q000737:chemistry*; D006096:Gramicidin / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D010446:Peptide Fragments / Q000737:chemistry*; D011392:Proline / Q000737:chemistry*; D017433:Protein Structure, Secondary; D012997:Solvents / Q000737:chemistry; D013141:Spiro Compounds / Q000737:chemistry; D013237:Stereoisomerism
D010446:Peptide Fragments; D012997:Solvents; D013141:Spiro Compounds; D006096:Gramicidin; D011392:Proline; D005947:Glucose