Investigation of the Binding Determinants of Phosphopeptides Targeted to the Src Homology 2 Domain of the Signal Transducer and Activator of Transcription 3. Development of a High-Affinity Peptide Inhibitor was written by Coleman, David R.;Ren, Zhiyong;Mandal, Pijus K.;Cameron, Arlin G.;Dyer, Garrett A.;Muranjan, Seema;Campbell, Martin;Chen, Xiaomin;McMurray, John S.. And the article was included in Journal of Medicinal Chemistry in 2005.COA of Formula: C21H21NO4 The following contents are mentioned in the article:
As part of their research on the design of Src homol. 2 (SH2) directed peptidomimetic inhibitors of Stat3, the authors, here, describe structure-activity relationship studies that provide information on the nature of peptide-protein interactions of a high-affinity phosphopeptide, Ac-Tyr(PO3H2)-Leu-Pro-Gln-Thr-Val-NH2 (peptide 1), inhibitor of Stat3 dimerization and DNA binding. There is a hydrophobic surface on the SH2 domain that can accommodate lipophilic groups on the N-terminus. Of the amino acids tested, leucine provided the highest affinity at pY+1 and its main chain NH is involved with a hydrogen bond with Stat3, presumably Ser636. Cis-3,4-Methanoproline is optimal as a backbone constraint at pY+2. The side chain amide protons of Gln are required for high-affinity interactions. The C-terminal dipeptide, Thr-Val, can be replaced with groups ranging in size from Me to benzyl. The authors synthesized a phosphopeptide incorporating groups that provided increases in affinity at each position. Thus, Ph(CH2)2CO-Tyr(PO3H2)-Leu-cis-3,4-methanoPro-Gln-NHCH2Ph was the highest affinity peptide, exhibiting an IC50 of 125 nM vs. 290 nM for peptide 1 in a fluorescence polarization assay. This study involved multiple reactions and reactants, such as (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5COA of Formula: C21H21NO4).
(S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5) belongs to piperidine derivatives. Piperidine is a metabolite of cadaverine, a polyamine found in the human intestine. Industrially, piperidine is produced by the hydrogenation of pyridine, usually over a molybdenum disulfide catalyst. Pyridine can also be reduced to piperidine via a modified Birch reduction using sodium in ethanol.COA of Formula: C21H21NO4
Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem