Cyclisation reactions on pentapeptides containing the turn promoting residues Gly and Pro are investigated. Although the cyclisation reaction is fast, solvent-dependent mixtures of cyclic penta- and decapeptides are observed. NMR studies suggest a strong dependence of the monomer/dimer ratio on the cis-trans isomerisation found in linear and cyclic peptides. The critical influence on ring closure of a cis Xaa-Pro peptide bond conformation is demonstrated by using the cis peptide bond-inducing residue 2,2-dimethyl-1,3-thiazolidine-4 carboxylic acid (Dmt, pseudo-proline) as proline substitute. The results shed new light on the role of cis-trans isomerisation in pentapeptide cyclisation. (C) 1999 Elsevier Science Ltd. All rights reserved.