Synthesis of a new dipeptide template, its X-ray structure, and modeling studies on its conformational features.
The diastereoselective synthesis is reported of a dipeptide template which is closely related to H-Gly-Trp-OH. Intramolecular bond formation between alpha-C of Gly and ring position 2 of the Trp unit has been achieved by a Pictet-Spengler-type electrophilic aromatic substitution. The absolute configuration of the N-Moc protected dipeptide template 9.2H2O was determined by single-crystal X-ray crystallography and found to be (2S,5S). The cis orientation of the amino and carboxy termini prompted us to investigate the potential of 9 as a beta-turn mimic. MD calculations on the model pseudopeptide Ac-Ala-Gly-Trp-Ala-NHMe 11 suggest that an unusually tight turn should be favoured rather than a beta-turn. The proper protective situation as a pre-requisite for the incorporation of the template into a peptide has been established, and comments about its chemical properties are given.
Esser
F
F
Department of Medicinal and Analytical Chemistry, Boehringer Ingelheim KG, Germany.
Carpy
A
A
Briem
H
H
Köppen
H
H
Pook
K H
KH
D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D004151:Dipeptides / Q000138:chemical synthesis*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D011487:Protein Conformation; D013237:Stereoisomerism; D013698:Templates, Genetic
D004151:Dipeptides