17554-34-6Relevant academic research and scientific papers
Acid-Stable Ester Linkers for the Solid-Phase Synthesis of Immobilized Peptides
Budě?ínsky, Milo?,Jirá?ek, Ji?í,Mitrová, Katarína,Pícha, Jan
, p. 1297 - 1306 (2020/07/04)
A series of N-terminally Fmoc-protected linkers of the general formula Fmoc-X?CO?O?Y?COOH have been prepared, where X is ?NH?CH2?CH2- or -p-(aminomethyl)phenyl- and Y is ?(CH2)n? (n is 1 or 4) or -p-(methyl)phenyl-. These linkers can easily be covalently attached via their C-terminal carboxyl group to a resin bearing a free amino group. After cleavage of the N-terminal Fmoc group, the linkers can be extended by standard solid-phase peptide synthesis techniques. These ester linkers are acid-stable and resistant to the base-mediated diketopiperazine formation that often occurs during the synthesis of ester-bound peptides; they are stable at neutral pH in aqueous buffers for days but can be effectively cleaved with 0.1 m NaOH or aq. ammonia within minutes or hours, respectively. These properties make these ester handles well suited for use as linkers for the solid-phase peptide synthesis of immobilized peptides when the stable on-resin immobilization of the peptides and the testing of their biological properties in aqueous buffers at neutral pH are necessary.
Synthesis, bioactivity, docking and molecular dynamics studies of furan-based peptides as 20s proteasome inhibitors
Sun, Qi,Xu, Bo,Niu, Yan,Xu, Fengrong,Liang, Lei,Wang, Chao,Yu, Jiapei,Yan, Gang,Wang, Wei,Jin, Hongwei,Xu, Ping
, p. 498 - 510 (2015/03/18)
Proteasome inhibitors are promising compounds for a number of therapies, including cardiovascular and eye diseases, diabetes, and cancers. We previously reported a series of furanbased peptidic inhibitors with moderate potencies against the proteasome b5 subunit, hypothesizing that the C-terminal furyl ketone motif could form a covalent bond with the catalytic residue, threonine 1. In this context, we describe further optimizations of the furan-based peptides, and a series of dipeptidic and tripeptidic inhibitors were designed and synthesized, aiming at improved potency and better solubility. Most of the tripeptidic inhibitors demonstrated improved potency and selectivity as b5 subunit inhibitors in both enzymatic and cellular assays, and good antineoplastic activities in various tumor cell lines were also observed. However, no inhibitory effects were observed for the dipeptidic compounds, which led us to presume that a noncovalent binding mode is adopted. Docking studies and molecular dynamics simulations were carried out to verify this presumption, with results showing that the distance between the furyl ketone motif and Thr1 is slightly too long to form covalent bond.
Highly stereoselective peptide modifications through Pd-catalyzed allylic alkylations of chelated peptide enolates
Deska, Jan,Kazmaier, Uli
, p. 6204 - 6211 (2008/02/13)
Deprotonation of peptides in the presence of zinc chloride gives rise to highly reactive nucleophiles that can be subjected to palladium-catalyzed allylic alkylation reactions. Excellent diastereoselectivities are obtained that are nearly independent of the allylic substrate used. By using this protocol, highly functionalized side chains can also be incorporated in excellent yields and selectivities. The stereochemicaloutcome of the reaction is exclusively controlled by the peptide chain as long as terminal π-allyl-palladium complexes are involved. Probably, there is a threefold coordination, at least, ofthe deprotonated peptide chain to the chelating zinc ion. In such metal peptide complexes, one face of the generated enolate is shielded by the side chain of the adjacent amino acid, thus directing the electrophilic attack onto the opposite face. This behavior explains why an S amino acid always generates an R amino acid (and the other way round).
Syntheses of amino alcohols and chiral C2-symmetric bisoxazolines derived from O-alkylated R-4-hydroxyphenylglycine and S-tyrosine
Caplar, Vesna,Raza, Zlata,Katalenic, Darinka,Zinic, Mladen
, p. 23 - 36 (2007/10/03)
Chiral C2-symmetric bisoxazolines 1b-f and 2b,c, derived from 4′-O-alkylated R-4-hydroxyphenylglycine or S-tyrosine, were prepared. As intermediates, a series of chiral amino alcohols possessing substituted phenolic groups was prepared and fully characterized.
Novel non-peptide GPIIb/IIIa antagonists: Synthesis and biological activities of 2-[4-[2-(4-amidinobenzoylamino)-2-(substituted)acetyl]-3-(2-methoxy-2- oxoethyl)-2-oxopiperazinyl] acetic acids
Kitamura,Fukushi,Miyawaki,Kawamura,Terashita,Sugihara,Naka
, p. 258 - 267 (2007/10/03)
To improve the in vitro and in vivo potency of our first low molecular weight GPIIb/IIIa antagonist 1 (TAK-029), a series of 2-[4-[2-(4-amidinobenzoylamino)-2-(substituted)acetyl]-3-(2-methoxy-2- oxoethyl)-2-oxopiperazinyl]acetic acids were synthesized th
Synthesis of 6-Dimethylamino-9-[3'-(O-Methyl) (2S)-[UL-14C]Tyrosinylamino)-3'-Deoxy-β-D- ribofuranosyl] purine
Mehrotra, Amit P.,Ryan, Martin D.,Gani, David
, p. 623 - 634 (2007/10/03)
In order to investigate and further refine the mechanism of the unique cleavage activity of the 18 amino acid 2A region of the foot-and-mouth-disease virus (FMDV), the synthesis of 14C-labelled puromycin is required. Puromycin is an inhibitor of protein synthesis and is an analogue of the terminal aminoacyl-adenosine portion of aminoacyl-tRNA. A short and expedient four step synthesis of 6-dimethylamino-9-[3'-(O-methyl) (2S)-[UL-14C]tyrosinylamino)-3'-deoxy-β-D-ribofuranos purine (14C-labelled puromycin) starting from (2S)-[UL-14C]-tyrosine is therefore described.
A Formal Total Synthesis of the ACE Inhibitor K-13. An Application of Arene-Ruthenium Chemistry to Complex Chemical Synthesis
Pearson, Anthony J.,Lee, Kieseung
, p. 2304 - 2313 (2007/10/02)
Stoichiometric ruthenium activation of 4-chlorophenylalanine derivatives toward nucleophilic substitution, using phenoxide nucleophiles that are derived from protected dipeptides, allowed the formation of isodityrosine derivatives that are synthetic precursors to the ACE inhibitor K-13.An evaluation of carboxyl blocking groups revealed that a 2-bromoethyl ester is the most useful in terms of its compatibility with ruthenium complexation and subsequent nucleophile addition but that its removal is problematic.Conversion to iodoethyl ester using Finkelstein reaction conditions, in the presence of the peptide and amino acid functionality, provided a solution to this problem, since the iodoethyl group was easily removed on treatment with samarium diiodide.
Synthesis of oxazolidine derivatives of β-[3-(aryloxy)aryl]-α-amino acids by application of the diels-alder reaction
Olsen, Richard K.,Feng, Xianqi
, p. 5721 - 5724 (2007/10/02)
The Diels-Alder reaction has been used to construct the diaryl ether unit in oxazolidine derivatives of β-[3-(aryloxy)aryl]-α-amino acids. Cycloaddition of acetylenic ketone 6 with substituted aryloxy dienes, and subsequent aromatization, provided the tit
Tyrosine derivatives and use thereof
-
, (2008/06/13)
Novel O-alkyl tyrosine derivatives of low toxicity have the effect of enhancing absorption of pharmaceutically active substances such as peptides, administered by mouth or as a suppository: compounds of the invention are those of formula (I) below, esters and salts thereof wherein R1 is a lower alkyl group optionally substituted with an alkyloxy group; X is CO or SO2; -Y- is either a direct bond, lower alkylene group, substituted or unsubstituted vinylene group, or a group expressed as -CHR3-O- or -O-CHR3-; Ry is a substituted or unsubstituted phenyl group, naphthyl group or 2-benzo-furanyl group; R3 is either hydrogen or lower alkly group; or in the formula (I). R2-Y-X denotes N-benzyloxycarbonyl phenylalanyl, N-benzyloxycarbonyl-4-halogenophenylalanyl, or N-(m-methoxycinnamoyl) phenylalanyl group. ψψψ
