162648-54-6Relevant articles and documents
Remarkable Modulation of Self-Assembly in Short γ-Peptides by Neighboring Ions and Orthogonal H-Bonding
Jadhav, Sandip V.,Amabili, Paolo,Stammler, Hans-Georg,Sewald, Norbert
, p. 10352 - 10357 (2017)
Gabapentin, an antiepileptic drug, is known to form stable helical structures in short peptides. Distinctly, we report on the newly synthesized γ-analogue of gabapentin, that is, γ-gabapentin (γ-Gpn), which manifests β-sheet character at molecular and nanofibrous hydrogels at the supramolecular level. We investigated the influence of proximally immobilized cationic amino acids (lysine and arginine) on the self-assembly of backbone-expanded tripeptide motif. Interestingly, arginine was found to be superior, both physically and mechanically, over lysine in driving hydrogelation. We have concluded that intrinsic and biochemically distinct properties of the guanidinium ion of arginine (compared to ammonium ion of lysine) have contributed towards this effect. Furthermore, similar to pyroglutamyl (pGlu) modified amyloid β peptides, N-pGlu modification of our self-assembling tripeptide motif exerts a dramatic influence on aggregation and exhibits enhanced β-sheet character, accelerated self-assembly kinetics, improved optical transparency and provides higher mechanical stiffness to the peptide hydrogel.
Exploration of N-(2-aminoethyl)piperidine-4-carboxamide as a potential scaffold for development of VEGFR-2, ERK-2 and Abl-1 multikinase inhibitor
Jin, Feng,Gao, Dan,Wu, Qin,Liu, Feng,Chen, Yuzong,Tan, Chunyan,Jiang, Yuyang
, p. 5694 - 5706 (2013/09/12)
VEGFR, ERK and Abl had been respectively identified as good drug targets, and their crosstalk also had been well elaborated. Multitarget drugs were more advantageous for cancer treatment, however, no inhibitors simultaneously acting on the three proteins were developed due to their structural diversities. Herein, N-(4-((2-(2-(naphthaen-1-yl)acetamido)ethyl)carbamoyl)piperidin-4-yl)-6- (trifluoromethyl)nicotinamide (NEPT, 6a) was discovered as an active scaffold against VEGFR-2, ERK-2 and Abl-1 kinases through the combination of support vector machine, similarity searching and molecular docking. NEPT and its derivatives were synthesized by convenient routine, their in vitro anti-proliferative abilities against human liver cancer cell line HepG2 were preliminarily evaluated. A representative compound 6b showed an IC50 value of 11.3 μM and induced significant HepG2 cells apoptosis. Besides, these compounds displayed better anti-proliferative abilities against K562 cells (a cell line with typical hyperactivity of the above multikinases), for example compound 6b exhibited an IC50 value of 4.5 μM. Based on hepatotoxicity case reports of Abl inhibitors, cytotoxicity of synthetic compounds against normal liver cell lines (QSG7701 and HL7702) was studied, 6b had a similar toxic effect with positive control imatinib, and most compounds showed less than 35% inhibition activities at 100 μM. Molecular docking study disclosed interactions of 6b with VEGFR-2, ERK-2 and Abl-1 kinases, respectively. Our data suggested the biological activities of 6b may derived from collaborative effects of VEGFR-2, ERK-2 and Abl-1 inhibition.
Dipeptide nitriles
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Page column 25-26, (2010/02/05)
N-terminal substituted dipeptide nitriles as defined are useful as inhibitors of cysteine cathepsins, e.g. cathepsins B, K, L and S, and can be used for the treatment of cysteine cathepsin dependent diseases and conditions, including inflammation, rheumatoid arthritis, osteoarthritis, osteoporosis, tumors (especially tumor invasion and tumor metastasis), coronary disease, atherosclerosis (including atherosclerotic plaque rupture and destabilization). Particular dipeptide nitriles are compounds of formula I, or physiologically-acceptable and -cleavable esters or a salts thereof wherein: the symbols are as defined. In particular it has been found that by appropriate choice of groups R, R2, R3, R4, R5, X1, Y and L, the relative selectivity of the compounds as inhibitors of the various cysteine cathepsin types, e.g. cathepsins B, K, L and S may be altered, e.g. to obtain inhibitors which selectively inhibit a particular cathepsin type or combination of cathepsin types.
