83351-75-1

Upstream product

• 34619-03-9 tert-butyldicarbonate 
• 53559-18-5 (S)-2-amino-3-(4-hydroxyphenyl)propanamide hydrochloride 
• 24424-99-5 di-tert-butyl dicarbonate 
• 60-18-4 L-tyrosine 
• 3978-80-1 Boc-Tyr-OH 
• 7681-38-1 sodium hydrogen sulfate 
• 4326-36-7 (S)-N-(tert-butoxycarbonyl)tyrosine methyl ester 

Downstream Products

• 390815-93-7 Acetic acid 4-((S)-2-tert-butoxycarbonylamino-2-cyano-ethyl)-phenyl ester 
• 850080-01-2 [(S)-1-carbamoyl-2-(4-(prop-2-ynyloxy)phenyl)ethyl]-carbamic acid tert-butyl ester 
• 1593627-69-0 C₂₇H₃₃N₄O₄⁽¹⁺⁾*I^(1-) 
• 1593627-67-8 C₁₇H₂₅ClN₂O₄ 
• 17263-42-2 benzyl ((S)-1-(((S)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl)amino)-4-methyl-1-oxopentan-2-yl)carbamate 
• 53559-18-5 (S)-2-amino-3-(4-hydroxyphenyl)propanamide hydrochloride 
• 1596353-91-1 (S)-tert-butyl 2-((S)-2-tert-butoxycarbonylamino-3-(4-hydroxyphenyl)propionylamido)hex-3-enoate 
• 503157-87-7 O-[N-Boc-L-tyrosinyl-N,N-di-Boc-amide]-O-(S-pivaloyl-2-thioethyl)-3'-azido-3'-deoxythymidin-5'-yl phosphate 
• 503157-98-0 O-[N-(Boc)-L-tyrosinyl-N,N-di-Boc-amide]-O-(S-pivaloyl-2-thioethyl)-N,N-diisopropyl phosphoramidite 

Relevant academic research and scientific papers

α-Amino Diphenyl Phosphonates as Novel Inhibitors of Escherichia coli ClpP Protease

Increased Gram-negative bacteria resistance to antibiotics is becoming a global problem, and new classes of antibiotics with novel mechanisms of action are required. The caseinolytic protease subunit P (ClpP) is a serine protease conserved among bacteria that is considered as an interesting drug target. ClpP function is involved in protein turnover and homeostasis, stress response, and virulence among other processes. The focus of this study was to identify new inhibitors of Escherichia coli ClpP and to understand their mode of action. A focused library of serine protease inhibitors based on diaryl phosphonate warheads was tested for ClpP inhibition, and a chemical exploration around the hit compounds was conducted. Altogether, 14 new potent inhibitors of E. coli ClpP were identified. Compounds 85 and 92 emerged as most interesting compounds from this study due to their potency and, respectively, to its moderate but consistent antibacterial properties as well as the favorable cytotoxicity profile.

Comprehensive Synthesis of Amino Acid-Derived Thiazole Peptidomimetic Analogues to Understand the Enigmatic Drug/Substrate-Binding Site of P-Glycoprotein

A novel set of 64 analogues based on our lead compound 1 was designed and synthesized with an initial objective of understanding the structural requirements of ligands binding to a highly perplexing substrate-binding site of P-glycoprotein (P-gp) and their effect on modulating the ATPase function of the efflux pump. Compound 1, a stimulator of P-gp ATPase activity, was transformed to ATPase inhibitory compounds 39, 53, and 109. The ATPase inhibition by these compounds was predominantly contributed by the presence of a cyclohexyl group in lieu of the 2-aminobenzophenone moiety of 1. The 4,4-difluorocyclohexyl analogues, 53 and 109, inhibited the photolabeling by [125I]-IAAP, with IC50 values of 0.1 and 0.76 μM, respectively. Selected compounds were shown to reverse paclitaxel resistance in HEK293 cells overexpressing P-gp and were selective toward P-gp over CYP3A4. Induced-fit docking highlighted a plausible binding pattern of inhibitory compounds in the putative-binding pocket of P-gp. The current study underscores the stringent requirement by P-gp to bind to chemically similar molecules.

Photoinduced electron transfer-promoted debenzylation of phenylalanine and tyrosine derivatives using dicyanoarene

Photoinduced debenzylations of phenylalanine and tyrosine derivatives with dicyanoarenes afford glycine derivatives by the generation of radical cations. Despite the limited substrate scope, the radical cation of phenylalanine and tyrosine derivatives bearing both a carbamate (without an aromatic group) at the N-terminal and an amide at the C-terminal could promote the breaking C–C bond at the benzylic position by a photoinduced electron transfer. It is important to understand the chemical behavior of the radical cations of phenylalanine and tyrosine in enzymes involving electron transfer.

Rational design of a redox-labeled chiral target for an enantioselective aptamer-based electrochemical binding assay

A series of redox-labeled L-tyrosinamide (L-Tym) derivatives was prepared and the nature of the functional group and the chain length of the spacer were systematically varied in a step-by-step affinity optimization process of the tracer for the L-Tym aptamer. The choice of the labeling position on L-Tym proved to be crucial for the molecular recognition event, which could be monitored by cyclic voltammetry and is based on the different diffusion rates of free and bound targets in solution. From this screening approach an efficient electroactive tracer emerged. Comparable dissociation constants Kd were obtained for the unlabeled and labeled targets in direct or competitive binding assays. The enantiomeric tracer was prepared and its enantioselective recognition by the corresponding anti-D-Tym aptamer was demonstrated. The access to both enantiomeric tracer molecules opens the door for the development of one-pot determination of the enantiomeric excess when using different labels with well-separated redox potentials for each enantiomer. Trace compounds: Redox tracers have been synthesized for enantioselective electrochemical ligand binding assays by relying on the combined use of an oligonucleotide-aptamer receptor with the detection of the redox label. A rational step-by-step optimization procedure has been developed leading to a redox-labeled L-tyrosinamide derivative (see figure) conserving the high affinity towards the aptamer.

C-Terminally Pegylated Growth Hormones

Conjugated growth hormones of the structure (I) are provided together with methods for manufacturing said conjugates. The conjugates are useful in therapy.

COUPLING OF POLYPEPTIDES AT THE C-TERMINUS

The present invention relates to novel polypeptides, methods for their synthesis, pharmaceutical compositions comprising the novel polypeptides as well as their use in medicaments for therapeutic applications.

C-TERMINALLY PEGYLATED GROWTH HORMONES

7150.204-WO 141 ABSTRACT Conjugated growth hormones of the structure O NH2 GH Leu N H G PEG [I] are provided together with methods for manufacturing said conjugates. The conjugates are 5 useful in therapy.

S-acyl-2-thioethyl aryl phosphotriester derivatives of AZT: Synthesis, antiviral activity, and stability study

The synthesis, antiviral activity, and stability study of phosphotriester derivatives of 3′-azido-2′,3′-dideoxythymidine (AZT) bearing modified L-tyrosinyl residues are reported. These compounds were obtained via phosphoramidite (PIII) chemistr

Dichlorotris(dimethylamino)phosphorane as a Dehydratisation Reagent for the Preparation of N-Protected Amino Acid Amides

Besides for the synthesis of peptides and activated esters dichlorotris(dimethylamino)phosphorane (2) now proved to be an excellent reagent for the preparation of N-protected amino acid amides.