The B(OH)−NH Analog Is a Surrogate for the Amide Bond (CO−NH) in Peptides:  An ab Initio Study

• Published in: Journal of chemical theory and computation Vol. 3; no. 2; pp. 619 - 627
• Main Authors: Malde, Alpeshkumar K, Khedkar, Santosh A, Coutinho, Evans C
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 01.03.2007
• ISSN: 1549-9618; 1549-9626
• DOI: 10.1021/ct600256s

The conformational preferences of N-methyl-methylboronamide (NMB), a B(OH)−NH analog of the amide CO−NH in natural peptides, have been investigated at the Hartree−Fock; Becke's three-parameter exchange functional and the gradient-corrected functional of Lee, Yang, and Parr; and second-order Møller−Plesset levels of theory with the 6-31+G* basis set. The minima, saddle points, and rotation barriers on the potential energy surface of NMB have been located and the energy barriers estimated. Besides the global minimum, there are three local minima within 2.0 kcal mol-1 of the global minimum characterized by specific ω and τ torsion values. The energy barriers for rotation about the “ω angle” are 16.4−18.8 kcal mol-1 and are a consequence of the double-bond character of the B−N bond as revealed by natural bond orbitals calculations. The “ω angle” and the ω rotation barrier are nearly the same as those seen in natural peptides. The τ rotation barriers (B−O bond) are relatively low because of the single-bond character of the B−O bond. Ala-BON, the Ala-dipeptide derived from NMB, has been constructed as a model peptide to study the conformational preferences about the φ and ψ torsion angles. The study reveals a strong preference for α-helix, type-II β-turn, 2.27 ribbon, and antiparallel β-sheet conformations, and mirror images of both type-II β-turn and 2.27 ribbon motifs whose φ and ψ values fall in the “disfavored regions” of the Ramachandran map. Thus, the replacement of the carbonyl group by B−OH retains the geometry and barrier around the “ω angle” and induces a strong preference for regular secondary structure motifs and also structures with positive φ values. This makes the B(OH)−NH analog an important surrogate for the peptide bond, with the additional advantage of stability to proteolytic enzymes.