2280-68-4Relevant academic research and scientific papers
Active Site Mapping of Human CathepsinF with Dipeptide Nitrile Inhibitors
Schmitz, Janina,Furtmann, Norbert,Ponert, Moritz,Frizler, Maxim,L?ser, Reik,Bartz, Ulrike,Bajorath, Jürgen,Gütschow, Michael
, p. 1365 - 1377 (2015/08/03)
Cleavage of the invariant chain is the key event in the trafficking pathway of major histocompatibility complex classII. CathepsinS is the major processing enzyme of the invariant chain, but cathepsinF acts in macrophages as its functional synergist which is as potent as cathepsinS in invariant chain cleavage. Dedicated low-molecular-weight inhibitors for cathepsinF have not yet been developed. An active site mapping with 52 dipeptide nitriles, reacting as covalent-reversible inhibitors, was performed to draw structure-activity relationships for the non-primed binding region of human cathepsinF. In a stepwise process, new compounds with optimized fragment combinations were designed and synthesized. These dipeptide nitriles were evaluated on human cysteine cathepsinsF, B, L, K and S. Compounds 10 (N-(4-phenylbenzoyl)-leucylglycine nitrile) and 12 (N-(4-phenylbenzoyl)leucylmethionine nitrile) were found to be potent inhibitors of human cathepsinF, with Ki values 10nM. With all dipeptide nitriles from our study, a 3D activity landscape was generated to visualize structure-activity relationships for this series of cathepsinF inhibitors. Mapping with nitriles: For human cathepsinF, low-molecular-weight inhibitors have not been developed so far. Therefore, a library of 52 dipeptide nitriles, known to interact in a covalent but reversible manner with the active site cysteine, was evaluated for cathepsinF inhibition. With the kinetic data in hand, optimized candidates were designed, synthesized, and tested to improve the activity profile as cathepsinF inhibitors.
Kinetically Controlled Peptide Bond Formation in Anhydrous Alcohol Catalyzed by the Industrial Protease Alcalase
Chen, Shui-Tein,Chen, Shiah-Yun,Wang, Kung-Tsung
, p. 6960 - 6965 (2007/10/02)
The industrial alkaline protease alcalase has been found to be very stable (half life > 5 days in ethanol or 2-methyl-2-propanol) and active in alcoholic solvents (except methanol).Procedures have been developed for alcalase-catalyzed, kinetically controlled peptide bond formation in anhydrous alcohol (ethanol, 2-methyl-2-propanol).Studies of the selectivity of an alcalase-catalyzed reaction show that only L-amino acid acyl donors are substrates at the p-1 subsite of alcalase; at the p-1' subsite both D- and L-amino acid nucleophiles are substrates.Other amino compounds such as benzylamine and phenylhydrazine are good nucleophiles.Studies of the effect of the water content of the reaction solution on the yield in the synthesis of Moz-Phe-Leu-NH2 showed that the 95percent yield obtained in anhydrous 2-methyl-2-propanol was decreased to 48percent in 2-methyl-2-propanol containing 4.86percent water.
Bombesin receptor antagonists. 5 new irreversible alkylating analogues
De Castiglione,Gozzini,Galantino,Corradi,Ciomei,Roletto,Bertolero
, p. 855 - 867 (2007/10/02)
New alkylating bombesin analogues were synthesized in order to increase their solubility and stability in aqueous solutions. The best compromise between these parameters and the biological properties (receptor binding and antagonistic activity) was achieved with 4-[bis(2-chloro-ethylamino)]benzoyl derivatives of the BN (7-14) octapeptide carrying a (13-14) reduced peptide bond independently of the presence of a His12 residue, either free or protected.
SYNTHESIS OF C-TERMINAL FRAGMENTS OF BOMBESIN AND THEIR ANALOGUES
Kuranova, I. L.,Churkina, S. I.,Dyudmirova, V. L.,Filonova, E. B.,Ibatullin, F. M.,et al.
, p. 475 - 484 (2007/10/02)
With the aim of structural-functional studies in the bombesin series, a number of bombesin fragments and analogues have been synthesized.The synthesis was performed by the carbodiimide method and by the activated-ester method.Fragments with the sequences
Selective Cleavage of the Allyl and Allyloxycarbonyl Groups through Palladium-Catalyzed Hydrostannolysis with Tributyltin Hydride. Application to the Selective Protection-Deprotection of Amino Acid Derivatives and in Peptide Synthesis
Dangles, O.,Guibe, F.,Balavoine, G.,Lavielle, S.,Marquet, A.
, p. 4984 - 4993 (2007/10/02)
N-Allyloxycarbonyl (Alloc) derivatives of amines and amino acids are quantitatively and very rapidly converted to free amino compounds by palladium-catalyzed hydrostannolytic cleavage with tributyltin hydride in the presence of a proton donor (acetic acid, p-nitrophenol, pyridinium acetate, water).A similar procedure can be used for the deprotection of allyl (All) carboxylates and allyl aryl ethers.Deprotection experiments were performed on various mixed N-Alloc and O-Bzl, N-Z and O-All, N-Alloc and O-t-Bu, and N-alloc- and N-Boc-protected amino acid derivatives.The palladium-catalyzed hydrostannolytic cleavage is fully compatible with the Bzl and Z protecting groups; furthermore the BOC and t-Bu groups and the Alloc and All groups appear to be ortogonal.The reliability of the Alloc methodology for temporary protection of the α-amino functions is ilustrated by the solid-phase synthesis of the biologically active undecapeptide substance P.
PALLADIUM-CATALYZED REACTION OF TRIBUTYLTIN HYDRIDE. SELECTIVE AND VERY MILD DEPROTECTION OF ALLYL AND ALLYLOXYCARBONYL DERIVATIVES OF AMINO-ACIDS.
Guibe, F.,Dangles, O.,Balavoine, G.
, p. 2365 - 2368 (2007/10/02)
Allyl(All) and Allyloxycarbonyl(Alloc) amino-acid derivatives are deprotected through palladium-catalyzed hydrostannolysis by Bu3SnH in a highly selective manner.Benzyl and benzyloxycarbonyl groups are stable under these conditions.Moreover the allyl and Alloc groups seem orthogonal to the t-butyl and t-butoxycarbonyl protecting groups.
6,Pro9>SP6-11, a Selective Agonist for the Substance P-P-Receptor Subtype
Laufer, Ralph,Gilon, Chaim,Chorev, Michael,Selinger, Zvi
, p. 1284 - 1288 (2007/10/02)
Substitution of a single amino acid residue, proline for glycine-9 in 6>SP6-11, a hexapeptide analogue of substance P, confers on the peptide selective agonist activity toward the SP-P receptor subtype. 6,Prosu
