Tripeptides, cyclic, conformations

Contrary to the cyclic tripeptides, cyclic tetrapeptides are found as natural products such as chlamydocin,1208-2111 HC-toxin,1212-2131 WF 3161,1214,2151 or tentoxin,173,216-2191 which all exhibit interesting pharmacological properties, e.g. phytotoxic (HC-toxin and tentoxin) or can-cerostatic activities (chlamydocin) (Scheme 8). Correspondingly, this class of compounds has been studied extensively in terms of synthesis and conformational preferences. 

Cyclic tripeptides constitute a small, but well-defined class of cyclic structures that have been studied intensively in terms of synthetic accessibility and conformational properties, 1 although naturally occurring representatives have not, so far, been identified. 

Table 1 The Possible Conformations of Cyclic Tripeptides Depend upon the Chirality of the Amino Acid Residues 45,46 ...

Thaisrivongs, S., Blinn, J.R., Pals, D.T. and Turner, S.R. (1991) Conformationally constrained renin inhibitory peptides cyclic (3-l)-l-(carboxymethyl)-L-prolyl-L-phenylalanyl-L-histidinamide as a conformational restriction at the P2-P4 tripeptide portion of the angiotensinogen template, J. Med. Chem. 34 1276-1282. 

The dipole moments of several different-sized saturated lactones have been measured, and the results interpreted in terms of the proportions of s-cis and s-trans conformers present in solution. The dipole moment of caprylolactone in benzene is 2.25 D, and it was suggested to exist as a mixture of both conformers <58AG312,59T253). The dipole moment of the crown ether (68) has been measured as 1.55 D in benzene <74CC243>, and 4,4,7,7-tetramethyloxan-2,9-dione (75) has a dipole moment of 4.1 D in benzene <74ACS(B)13>. The cyclic tripeptide (50) has a dipole moment of 4.66 D in benzene <69CC656>. 

In cyclic dipeptides, the peptide groups are constrained to the cis conformation. Cyclic tripeptides also require cis peptide groups, whereas in cyclic tetra- and pentapeptides a transition takes place between a variety of confer-... 

M. Rothe, W. Schindler, R. Pudill, U. Kostrzewa, R. Theyson, R. Steinberger, Zum Problem der Cyclotripeptidsynthese, Peptides, Proc. 11th Europ. Pept. Symp. Wien 1971, 388-399 M. Rothe, K.-L. Roser, Conformational flexibility of cyclic tripeptides, Abstr. 20th Europ. Pept. Symp. Tubingen 1988, p. 36... 

Dory and co-workers synthesized a tripeptide composed of a, -unsaturated (5-amino acids (Fig. 8.10a) [45]. The trans geometry of the vinyl group was used to induce the peptide to adopt a flat conformation required for the self-assembling process. In a similar way to the nanombes from y5-peptides, the peptide backbone has an even number of atoms between the carbonyl and amino groups of each residue. As a result, all the hydrogen bonds were parallel in the nanotube (Fig. 8.10b). The same group further extended this pattern to di-, tri-, and tetrapeptides of -amino acids with a trans yS,(5-double bond (Fig. 8.10c). AU of these cyclic peptides were found to self-assemble into hydrogen bonded nanotubes [46]. 

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