1. Structure of a Gla-containing dipeptide. The crystal structure of (+/-)-N-carbobenzoxy-(gamma,gamma'-DI-tertbutyl)-gamma-carboxyglutamylglycine ethyl ester
E J Valente, R G Hiskey, D J Hodgson Biochim Biophys Acta. 1979 Aug 28;579(2):466-8. doi: 10.1016/0005-2795(79)90074-6.
The crystal and molecular structure of a dipeptide containing a blocked gamma-carboxyglutamyl (Gla) residue is presented. Two intermolecular hydrogen bonds link the amides with carbonyl groups in the dipeptide backbone, but the protected gamma-carboxy groups on the modified glutamic acid are not hydrogen bonded.
2. Synthesis of potent antagonists of substance P by modifying the methionyl and glutaminyl residues of its C-terminal hexapeptide and without using D-amino acids
A Manolopoulou, K Karagiannis, G Stavropoulos, C Poulos, C C Jordan, R M Hagan Int J Pept Protein Res. 1993 Apr;41(4):411-4. doi: 10.1111/j.1399-3011.1993.tb00458.x.
Analogues of [Orn6]-SP6-11 have been synthesized in which the Met11-NH2 residue is replaced by the alpha, gamma-dimethyl, alpha, gamma-dibenzyl and alpha, gamma-di-tert-butyl esters of glutamic acid. These analogues were tested in three in vitro preparations representative of NK-1, NK-2 and NK-3 receptor types for agonist and antagonist activity. The dimethyl analogue is a selective full agonist in the NK-1 receptor type and a weak antagonist in the other two receptor types, while the dibenzyl and the di-tert-butyl analogues are potent antagonists in the NK-1 receptor type and weak antagonists in the other two receptor types. It is concluded that appropriate modification at the alpha-carboxamide and the side chain of the methionine residue of substance P may induce antagonism without using D-amino acids.
