Synthesis of model compounds, first of all those which can be used to get new knowledge in bioorganic chemistry, stereochemistry, theoretical chemistry, catalysis
Model compounds are studied by scientists as simple surrogates of very complex objects, for example, enzymes. Several basic principles in the design of model compounds and research tools were implemented, which might be beneficial for a particular scientific objective. The main design is conformational restriction, or molecular rigidity. A few examples from the large “collection” of the synthesized models are:
- “most twisted amides” – 1-azaadamantan-2-one derivatives. Regarded at first a lab curiosity, twisted amides shed light onto important biochemical processes where the C-N bonds in peptides and proteins twist or rotate. This work is being done in collaboration with the University of Cambridge, University Chemical Laboratory.
compounds modelling hydrolytic amide bond cleavage. Several compounds mimicking either intermediates or enzyme active sites were synthesized. Important hypotheses were proven concerning enzymatic cleavage of amide linkage.
photoisomerizable model peptides, capable of switching between conformationally restricted and flexible forms under light-irradiation. The photoisomerization of model peptides was used to elucidate effect of conformational restriction on structure and properties of antimicrobial peptides in biomembranes.
I.V. Komarov, S.Yanik, A.Yu. Ishchenko, J.E. Davies, J.M. Goodman, A.J. Kirby. The Most Reactive Amide as a Transition-State Mimic For cis−trans Interconversion. J. Am. Chem. Soc. 2015, 137, 926−930.
I.V. Komarov, A.Yu. Ishchenko, A. Hovtvianitsa, V. Stepanenko, S. Kharchenko, A.D. Bond, A.J. Kirby. Fast Amide Bond Cleavage Assisted by a Secondary Amino and a Carboxyl Group – A Model for yet Unknown Peptidases? Molecules 2019, 24(3), 572.
O. Babii, S. Afonin, T. Schober, I.V. Komarov, A.S. Ulrich. Flexibility vs rigidity of amphipathic peptide conjugates when interacting with lipid bilayers. BBA – Biomembranes 2017, 1859, 2505–2515