β2-Amino Acids in the Design of Conformationally Homogeneous cyclo-Peptide Scaffolds
2006 (English)In: Journal of Organic Chemistry, ISSN 0022-3263, E-ISSN 1520-6904, Vol. 71, no 18, 6814-6821 p.Article in journal (Refereed) Published
Herein, we report studies on the influence of chiral, beta(2)-amino acids in the design of conformationally homogeneous cyclic tetrapeptide scaffolds. The cyclic alpha-tetrapeptide cyclo(-Phe-D-Pro-Lys-Phe-) (1) and its four mixed analogues, having one of the alpha-Phe replaced by either an (S)-or an (R)-beta(2)hPhe residue (i.e., cyclo(-(R)-beta(2)hPhe-D-Pro-Lys-Phe) (2a), cyclo(-(S)-beta(2)hPhe-D-Pro-Lys-Phe-) (2b), cyclo(-Phe-D-Pro-Lys-(R)-beta(2)hPhe-) (3a), and cyclo(- Phe- D- Pro- Lys-( R)-, 2hPhe-) ( 3b)), were all synthesized through solidphase procedures followed by solution- phase cyclization. Initially, all five cyclo- peptides were analyzed by H-1 NMR spectroscopic studies in different solvents and at variable temperatures. Subsequently, a detailed 2D NMR spectroscopic analysis of three of the mixed peptides in water was performed, and the information thus extracted was used as restraints in a computational study on the peptides' conformational preference. An X- ray crystallographic study on the side chain- protected (Boc) 2a revealed the solid- state structure of this peptide. The results presented herein, together with previous literature data on beta(3)-amino acid residues, conclusively demonstrate the potential of beta-amino acids in the design of conformationally homogeneous cyclic peptides that are homologous to peptides with known applications in biomedicinal chemistry and as molecular receptors.
Place, publisher, year, edition, pages
2006. Vol. 71, no 18, 6814-6821 p.
IdentifiersURN: urn:nbn:se:uu:diva-95283DOI: 10.1021/jo060854nISI: 000240020100013PubMedID: 16930031OAI: oai:DiVA.org:uu-95283DiVA: diva2:169442