Conformations of cyclo(L‐alanyl‐L‐alanyl‐ε‐aminocaproyl) and of cyclo(L‐alany1‐D‐alanyl‐ε‐aminocaproyl); cyclized dipeptide models for specific types of β‐bends

Abstract

Conformational energy calculations indicate that the peptide backbones of the low‐energy conformations of the cyclized dipeptide derivatives cyclo (L‐alanyl‐L‐alanyl‐ε‐aminocaproyl) and cyclo (L‐alanyl‐D‐alanyl‐ε‐aminocaproyl) are constrained to form β‐bends of types I + III and II, respectively. Thus, the two compounds can serve as models for the spectroscopic properties of β‐bends of these types. The coupling constants obtained from 1H n.m.r. spectra in DMSO‐d6 are consistent with the dihedral angles of the computed lowest‐energy conformations. Differences in 13C chemical shifts between the two compounds can be correlated with differences in shielding by C=O groups in bends of various types. 1H and 13C chemical shifts suggest association of cyclo (L‐Ala‐L‐Ala‐Aca) but not of cyclo (L‐Ala‐D‐Ala‐Aca) in dimethylsulfoxide. The different tendencies to associate can be explained in terms of the difference in conformation. The circular dichroism spectra of the two compounds are quite different. In methanol, trifluoroethanol and water, the L‐Ala‐L‐Ala derivative has a positive extremum near 190 nm and two negative extrema near 206 and 220 nm, whereas the L‐Ala‐D‐Ala derivative has a positive extremum at about 203 nm and negative extrema at about 187 and 229 nm. The spectra can be used to estimate the contribution of various bend types in a related series of compounds. A normal mode analysis of the vibrations of the computed low‐energy conformations was compared with solid state infrared and Raman spectra, in order to determine the predominant conformations. The bend types determined by this comparison fully agree with the predictions of the theoretical computations for both derivatives.

Electronic Circular Dichroism of the Cas9 Protein and gRNA:Cas9 Ribonucleoprotein Complex

“…These motifs constitute as the third most common secondary structural elements occurring in proteins. For example, the type I reveals α-helix-like ECD spectrum, while the type II shows a β-sheet-like one, what was confirmed experimentally [47]. The Cas 9 has β-turn motifs in its structure, what may be manifested in reduced intensity of the positive band at 196 nm, as well as in a gentle difference in intensity between negative ECD bands ([θ]221/[θ]209 = 1.12).…”

Characterization of β-turns by electronic circular dichroism spectroscopy: a coupled molecular dynamics and time-dependent density functional theory computational study

“…41 Although ECD experiments were not recorded below 190 nm, the obtained pattern resembles class B of Woody's classification (Table II). Similarly, Bandekar et al observed 44 a class B ECD spectra, with a minimum below 188 nm, a maximum at 202-204 nm and another minimum around 228-230 nm, for the cyclo(L-Ala-D-Ala-Aca) peptide forming a type II β-turn. In the same study, a class C pattern (a maximum near 190 nm and two distinct minima at 206-208 and 218-222 nm) was observed for the cyclo(L-Ala-L-Ala-Aca) peptide that exhibits a type I (and III) β-turn.…”

“…40 The third and most used approach relies on the comparative structural studies of peptides by ECD, NMR and X-ray crystallography. 28,29,[41][42][43][44] In this approach, cyclic or modified aminoacid peptides were used to restrain the flexibility of the molecules. For instance, ECD spectra, composed by a negative band at 227-222 nm and a positive one at 200-205 nm, were observed for cyclic hexapeptides (cyclo(Gly/Orn-L-Pro-D-Phe/Cha) 2 ) adopting a type II β-turn geometry.…”

A significant role for high‐energy transitions in the ultraviolet circular dichroism spectra of polypeptides and proteins

“…Figure 1 shows the characteristic CD spectra of four important polypeptide conformations-the a-helix, b-sheet, b-turn, and unordered conformations. 3,21,22 Exciton theory neglecting contributions of high-energy transitions gives a good explanation for the a-helix, 23 b-sheet, 16,24 and bturn 25 CD spectra, but not for the unordered conformation. 26,27 Of course, the unordered conformation is actually an ensemble of many conformers and that seriously complicates prediction of its CD spectrum.…”

“…a-helix (no symbols), poly(Glu) in water, pH 4.5 3 ; b-sheet (~), poly(Lys-Leu), 0.5 M NaF, pH.7 21 ; type I b-turn (! ), cyclo(L-Ala-L-Ala-Aca) in water, pH 7 (Aca 5 e-aminocaproic acid) 22 ; unordered (l), poly(Glu) in water, pH 8. 3 band near 175 nm, where the CD of poly(Pro)II is negative.…”