Amides binding modes

The insertion of histidine in position two of the peptide chain results in the simultaneous binding of the N-terminal amine, the imidazole, and the intervening amide-N to the Ni11 ion. The major complex [NiH iL]+ with NH2,N am,Nim binding mode is pseudo-octahedral and in... 

Fig. 5.20. Modes of coordination of transition metal ions with /3-lactam antibiotics. Complex A In penicillins, the metal ion coordinates with the carboxylate group and the /3-lactam N-atom. This complex stabilizes the tetrahedral intermediate and facilitates the attack of HO-ions from the bulk solution. Complex B In benzylpenicillin Cu11 binds to the deprotonated N-atom of the amide side chain. The hydrolysis involves an intramolecular attack by a Cu-coordinated HO- species on the carbonyl group. Complex C In cephalosporins, coordination of the metal ion is by the carbonyl O-atom and the carboxylate group. Because the transition state is less stabilized than in A, the acceleration factor of metal ions for the hydrolysis of cephalosporins is lower than for penicillins. Complex D /3-Lactams with a basic side chain bind the metal ion to the carbonyl and the amino group in their side chain. This binding mode does not stabilize the tetrahedral transition complex and, therefore, does not affect the rate of... 

Brecx, V, Papeleu, P., Iterbeke, K., Geerlings, P. et al. (2003) Amide analogues of TSA Synthesis, binding mode analysis and HDAC inhibition. Bioorganic S, Medicinal Chemistry Letters, 13, 1861-1864. 

Guo, Y., Xiao, J., Guo, Z Chu, F., Cheng, Y. and Wu, S. (2005) Exploration of a binding mode of indole amide analogues as potent histone deacetylase inhibitors and 3D-QSAR analyses. Bioorganic and Medicinal Chemistry, 13, 5424—5434. 

Fig. 10.3. Adamantyl amide analogs exhibit similar binding modes in guinea pig (green) and in human (pink) 11 (S-HSD1 cocrystal complexes, with Ser-170 and Tyr-183 forming hydrogen bond interactions with the bound ligands. A nonconserved residue (Tyr-231 in guinea pig and Asn-123 in human) differentiates the active sites for these analogs.

---