All-cis Cyclic Peptides

Abstract

Amide bonds -NH-CO- preferentially exist in trans conformations, the cis conformation being thermodynamically unfavored with respect to the trans by about 2 kcal/mol. Yet, the main reason most proteins or peptides cannot be made from cis-peptide plaques only lies in that connecting them into open chains appears to be sterically impracticable. It is possible, however, to build all-cis cyclic peptides in which all cis-plaques are efficiently locked. The present work examines, through quantum calculations, the structural and energetic issues associated with these peculiar arrangements. Systematic exploration at DFT-B3LYP level of the potential-energy surfaces for all-cis cyclopolyglycines cG(n)(c) (n = 2-10,15), and to a lesser extent, for all-cis cyclopolyalanines and all-cis cyclopolyphenylalanines confirms that all these structures are true minima. Optimal ring size occurs around eight peptide units, resulting in planar cG7(c), cG8(c), and cG9(c). In smaller systems, the ring strain is relieved through nonplanar cup-like distortions, particularly in cG6(c). From 10 peptide units and beyond, the ring framework distorts into a saddle-edge shape. These molecules disclose some molecular flexibility, as combinatorial tilting of the plaques may give sets of minima close in energy. Indexes based on isodesmic reactions are used to estimate the energy for joining all-cis or all-trans plaques into cyclic peptides. One of them, the mean plaque-junction energy (MPJE) suggests that within sensible sizes from six peptide units and beyond, all-cis plaque association is almost equally favorable as all-trans one. The frame of radiating cis-amide bonds can be considered as defining a new kind of peptidic material, endowed with specific self-assembling properties.

Cyclization-activated Prodrugs

“…Intramolecular cyclization has been demonstrated to improve biological properties of bioactive peptides [28][29][30][31][32][33][34][35][36][37][38], in many cases allowing one to improve selectivity for a given receptor and/or metabolic stability [39][40][41]. Cyclic peptides can be divided into homodetic and heterodetic, the first being obtained by formation of an intramolecular peptide (amide) bond, whereas heterodetic refers to all cyclic peptides where the intramolecular bond newly formed is other than an amide (e.g., lactone, ether, thioether and, most commonly, disulphide bridges).…”

Selective Complexation of S‐block Cations with Nanotubular Silk Type Cyclopeptides: A DFT Study

“…In the present study, six cyclic silk type structures named Silk1, Silk2, Silk3, Silk4, Silk5 and Silk6 has been considered where all cyclic peptides are in their cis configuration. 7 The structures were constructed from the alternate junction of alanine and glycine amino acids. The Silk1 and Silk2 structures constructed from three alanine and glycine molecules alternately.…”

“…The initial geometries of cyclic peptides were taken from the structures reported by Poteau and Trinquier. 7 Vibrational frequency calculations were also performed to verify that the optimized structures are in the local minimum on the potential energy surface. All Calculations were performed with the GAUSSIAN 09 program package.…”

Interaction of metal ions with cyclo[(1R,3S)-γ-Acc-Gly]3 hexapeptide – A theoretical study

“…1 that the (TAG) 3 structure is flat with C@O and NAH groups lying roughly perpendicular to the peptidic plane. The valence angle (a) is known to be an important parameter in describing the structure of cyclic peptides [50,33]. Hence in this study, in order to understand the structural propensities of (TAG) 3 , we have made use of a along with the peptide deformation angles x, which are given in Table 1.…”