80975-50-4

Upstream product

• 24424-99-5 di-tert-butyl dicarbonate 
• 38658-15-0 (S)-2-amino-6-(benzyloxy)-6-oxohexanoic acid 
• 1118-90-7 L-homoglutamic acid 
• 100-51-6 benzyl alcohol 
• 108312-38-5 N^α,N^ε-di-tert-butyloxycarbonyl-L-lysine 2,2,2-trichloroethyl ester 
• 108312-35-2 N^α,N^ca-di-tert-butyloxycarbonyl-L-homoglutamine 
• 20194-18-7 sodium phenyl-methanolate 
• 58632-95-4 2-(tert-Butoxycarbonyloxyimino)-2-phenylacetonitrile 

Downstream Products

• 171270-54-5 (3S)-3-[(2S)-5-benzyloxycarbonyl-2-(tertiarybutoxycarbonylamino)-pentanoyl]oxyhexadecanamide 
• 124184-51-6 C₂₂H₂₈N₂O₈ 
• 77302-98-8 (S)-2-[(S)-5-Benzyloxycarbonyl-2-((S)-5-benzyloxycarbonyl-2-tert-butoxycarbonylamino-pentanoylamino)-pentanoylamino]-4-methyl-pentanoic acid methyl ester 

Relevant academic research and scientific papers

CASPASE INHIBITORS AND METHODS OF USE THEREOF

Provided herein are compounds of formula (I), compositions comprising the compounds and method of treating various diseases with the compounds and compositions.

Potent and fully noncompetitive peptidomimetic inhibitor of multidrug resistance P-glycoprotein

Nα-Boc-l-Asp(OBn)-l-Lys(Z)-OtBu (reversin 121, 1), an inhibitor of the P-gp ABC transporter, was used to conceive compounds inhibiting the drug efflux occurring through the Hoechst 33342 and daunorubicin transport sites of P-gp, respectively H and R sites. Replacement of the aspartyl residue by trans-4-hydroxy-l-proline (4(R)Hyp) gave compounds 11 and 15 characterized by half-maximal inhibitory concentrations (IC50) of 0.6 and 0.2 μM, which are 2-and 7-fold lower than that of the parent molecule. The difference in IC50 between 11 and 15 rests on the carbonyl group of the peptidyl bond, reduced in 15. Those compounds are rather specific of P-gp, having no or limited activity on MRP1 and BCRP. 15 displayed no marked cytotoxicity up to 10-fold its IC50. Importantly, 15 equally inhibited the Hoechst 33342 and daunorubicin effluxes through a typical noncompetitive inhibition mechanism, suggesting its binding to a site different from the H and R drug-transport sites.

Synthesis and biological evaluation of boron peptide analogues of Belactosin C as proteasome inhibitors

A series of boron peptides 11, 13, 15 and 17 were designed and synthesized as proteasome inhibitors based on the structure of Belactosin C. Matteson homologation was a key step in the synthesis of the boron peptides. Compounds 11a and 13 showed significant inhibition of 20S proteasome chymotrypsin-like (β5) activity (IC50 = 0.28 and 0.51 μM, respectively). Furthermore, like PS-341, compound 11a increased the G2/M cell distribution. A biparametric cytofluorimetric analysis with FITC-labeled annexin V and propidium iodide showed induction of apoptosis by compound 11a at >1 μM concentrations of compound.

PROPERTIES OF Nα,Nca-DI-TERT-BUTYLOXYCARBONYL-ω-CARBAMOYL-α-AMINO ACIDS AND DIRECT SYNTHESIS OF PROTECTED HOMOGLUTAMIC ACID DERIVATIVES

The protected carboxamide function of Nα,Nca-di-tert-butyloxy-carbonyl-ω-carbamoyl-α-amino acids worked well with nucleophilic reagents.Applying this novel reactivity, we developed an efficient synthetic route to Nα-tert-butyloxycarbonylhomoglutamic acid and its derivatives, including Nα-tert-butyloxycarbonylhomoglutamic acid δ-benzyl ester, from Nα,Nca-di-tert-butyloxycarbonylhomoglutamine.KEYWORDS - protected homoglutamic acid synthesis; Nca-tert-butyloxycarbonylated carboxamide; hydrolysis; selective deprotection; Nα-tert-butyloxycarbonylhomoglutamic acid δ-benzyl ester; Nα-tert-butyloxycarbonylhomoglutamic acid α-tert-butyl ester; Nα-tert-butyloxycarbonylhomoglutamine; optical purity

Synthesis of Peptide Analogues of Prothrombin Precursor Sequence 5-9. Substrate Specificity of Vitamin K Dependent Carboxylase

Thirty-five analogues of Phe-Leu-Glu-Glu-Leu, the pentapeptide sequence 5-9 of bovine prothrombin precursor, were synthesized and assayed as potential substrates or inhibitors of rat liver vitamin K dependent carboxylase.Carboxylation of substrate was determined by measuring the incorporation of carbon-14 labeled bicarbonate into product.Changes in substrate carboxylation produced by changing peptide chain length, amino acid chirality, or the distance seperating the peptide chain backbone from the carboxyl group were measured.The data suggest that the carboxylase carboxylates L-glutamic acid residues and does not carboxylate L-aspartic acid, L-homoglutamic acid, glutamine, or D-glutamic acid residues; tri- through pentapeptides are better substrates than mono- or bis(amino acid) derivatives, and hydrophobic groups added to the N-terminus can produce better substrates for the enzyme.None of the synthetic substrates is carboxylated as effectively as the endogenous protein substrates for the enzyme.The effect of structure on additional parameters affecting carboxylation is discussed.