Avtor/Urednik		Breznik, Matej; Kikelj, Danijel
Naslov		Mimetiki prolina in cis/trans izomerizacija peptidne vezi prolina
Prevedeni naslov		Surrogates of proline and cis/trans isomerization of proline peptide bond
Tip		članek
Vir		Farm Vestn
Vol. in št.		Letnik 51, št. 4
Leto izdaje		2000
Obseg		str. 553-9
Jezik		slo
Abstrakt		Proline is the only naturraly occuring cyclic amino acid. Proline incorporated in a biologically active compound because of a bulky pyrrolidine ring restricts the local conformational freedom. This leeds to altered molecular felxibility and lowers the number of possible conformers. Naturally occuring amino acids predominatly form trans peptide bonds with exception of proline, which well-known facet is its ability to form cis peptide bonds and udergo cis/trans isomerization. Isomerization barrier of peptide bonds in proline containing molecules is lowered due to concomitant pyrolidine puckering changes; additionally, the trans conformation is favored only slightly over the cis bond. Because of these unique properties proline plays an important role in biological processes, biologically active and pharmaceutically important peptides and peptide mimetics. Numerous surrogates,mimetics and analogues of proline were developed and used in the synthesis of biologically active compounds with the aim to alter the cis/trans ratio of proline peptide bonds, to constrain the conformation of peptide bond and to produce proline like turns.
Izvleček		Prolin je edina naravna ciklična aminokislina, kar je razlog, da se njene lastnosti razlikujejo od lastnosti drugih naravnih aminokislin. Pirolidinski obroč, v katerega je zaprt aminski dušik, zmanjša konformacijski prostor peptidov, ki vsebujejo prolin. Zvijanje pirolidinskega obroča doprinese k zmanjšanju energetske razlike med cis in trans konformacijo peptidne vezi prolina, zaradi česar peptidna vez prolina izomerizira. Pogostost cis amidnih vezi je v peptidih, ki vsebujejo prolin, v primerjavi z drugimi aminokislinami neobičajno visoka. Proces cis/trans izomerizacije je pomemben pri mnogih biokemijskih procesih, pri katerih so udeleženi polipetidi, je pa nezaželjen v primeru kratkih linearnih peptidov in peptidomimetikov. Pri načrtovanju in razvoju različnih inhibitorjev so zato uporabili mimetike in analoge prolina, ki vplivajo na izomerizacijo in spremenijo razmerje med cis in trans konformerom peptidne vezi. V članku predstavljamo pregled tovrstnih mimetikov prolina.
Deskriptorji		PROLINE STEREOISOMERISM PROTEIN CONFORMATION