1. Synthesis and activity of HCO-Met-Leu-Phe-OMe analogues containing beta-alanine or taurine at the central position
Cesare Giordano, Gino Lucente, Marianna Nalli, Giampiero Pagani Zecchini, Mario Paglialunga Paradisi, Katia Varani, Susanna Spisani Farmaco. 2003 Nov;58(11):1121-30. doi: 10.1016/s0014-827x(03)00165-4.
New synthetic analogues of the chemotactic N-formyltripeptide HCO-Met-Leu-Phe-OMe have been synthesized. The reported new models, namely Boc-Met-beta-Ala-Phe-OMe (1), HCO-Met-beta-Ala-Phe-OMe (2), Boc-Met-Tau-Phe-OMe (3), HCO-Met-Tau-Phe-OMe (4) and HCl.Met-Tau-Phe-OMe (5), are characterized by the presence at the central position of a residue of beta-alanine or 2-aminoethanesulfonic acid (taurine) replacing the native L-leucine. Whereas tripeptides 1 and 2 have been found quite inactive as chemoattractants, all the three models containing the Tau residue exhibit a remarkable activity. Superoxide anion production and lysozyme release have been also evaluated and the biological results are discussed together with the conformational preferences of the examined models.
2. Kinetics of peptide synthesis studied by fluorescence of fluorophenyl esters
E A Permyakov, V N Medvedkin, L V Klimenko, Y V Mitin, S E Permyakov Jr Int J Pept Protein Res. 1994 Nov;44(5):472-6. doi: 10.1111/j.1399-3011.1994.tb00184.x.
The kinetics of the reaction of Boc-alanine-trifluorophenyl, Boc-alanine-tetrafluorophenyl, Boc-alanine-pentafluorophenyl, and Boc-alanine-p-chlorotetrafluorophenyl esters (BocAlaOTrf, BocAlaOTfp, BocAlaOPfp, and BocAlaTfc, respectively) with leucine amide and with valine methyl ester have been measured using changes in fluorophenyl chromophore emission at 375 nm. The kinetic data cannot be well fit with a simple second-order reaction scheme. Measurements of the reaction kinetics at different concentrations of the reagents showed that the expression for the reaction rate is V = kC(N)0.5C(AE)1.5, in which k is the reaction rate constant, CN is the concentration of either LeuNH2 or ValOCH3, and CAE is the concentration of the fluorophenyl ester. This reaction equation indicates a complex, probably chain-like, reaction mechanism. The order of reactivity for these active esters with ValOCH3 is BocAlaOTfc > BocAlaOPfp > BocAlaOTfp > BocAlaTrf. The apparent rate constant, k, for the reaction with LeuNH2 is higher than that for the reaction with ValOCH3.
3. Synthesis and biological activity of novel amino acid-(N'-benzoyl) hydrazide and amino acid-(N'-nicotinoyl) hydrazide derivatives
Sherine N Khattab Molecules. 2005 Sep 30;10(9):1218-28. doi: 10.3390/10091218.
The coupling reaction of benzoic acid and nicotinic acid hydrazides with N- protected L-amino acids including valine, leucine, phenylalanine, glutamic acid and tyrosine is reported. The target compounds, N-Boc-amino acid-(N;-benzoyl)- and N- Boc-amino acid-(N;-nicotinoyl) hydrazides 5a-5e and 6a-6e were prepared in very high yields and purity using N-[(dimethylamino)-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl- methylene]-N-methyl-methanaminium hexafluorophosphate N-oxide (HATU) as coupling reagent. The antimicrobial activity of the Cu and Cd complexes of the designed compounds was tested. The products were deprotected affording the corresponding amino acid-(N;-benzoyl) hydrazide hydrochloride salts (7a-7e) and amino acid-(N;- nicotinoyl) hydrazide hydrochloride salts (8a-8e). These compounds and their Cu and Cd complexes were also tested for their antimicrobial activity. Several compounds showed comparable activity to that of ampicillin against S. aureus and E. coli.
