A5017139184- Chemical Synthesis and Analysis
- Carbohydrate Chemistry and Synthesis
- Neuropeptides and Animal Physiology
- Enzyme Structure and Function
- Biochemical and Molecular Research
- Receptor Mechanisms and Signaling
- Cyclopropane Reaction Mechanisms
- Computational Drug Discovery Methods
- Mass Spectrometry Techniques and Applications
- Herpesvirus Infections and Treatments
- Click Chemistry and Applications
- Protein Structure and Dynamics
- Diabetes Treatment and Management
- Chemical Synthesis and Reactions
- Advanced Proteomics Techniques and Applications
- Asymmetric Hydrogenation and Catalysis
- Catalytic C–H Functionalization Methods
- Biotin and Related Studies
- Immune Response and Inflammation
- RNA Interference and Gene Delivery
- RNA and protein synthesis mechanisms
- Crystallization and Solubility Studies
- Biochemical Analysis and Sensing Techniques
- Synthesis and Catalytic Reactions
- Ubiquitin and proteasome pathways
Bristol-Myers Squibb (United States)
1997-2024
Merck & Co., Inc., Rahway, NJ, USA (United States)
1990-2020
Bristol-Myers Squibb (Germany)
1993-2014
Weatherford College
1993
University of Georgia
1986-1990
University of Padua
1984
The enzymatic β-C-H hydroxylation of the feedstock chemical isobutyric acid has enabled asymmetric synthesis a wide variety polyketides. analogous transition metal-catalyzed enantioselective functionalization acid-derived substrates should provide versatile method for constructing useful building blocks with enantioenriched α-chiral centers from this abundant C-4 skeleton. However, desymmetrization ubiquitous isopropyl moieties by organometallic catalysts remained an unanswered challenge....
Pd-catalyzed β-C–H functionalizations of carboxylic acid derivatives using an auxiliary as a directing group have been extensively explored in the past decade. In comparison to most widely used auxiliaries asymmetric synthesis, simplicity and practicality developed for C–H activation remains be improved. We previously simple N-methoxyamide direct activation, albeit this system was not compatible with acids containing α-hydrogen atoms. Herein we report development pyridine-type ligand that...
Proprotein convertase subtilisin/kexin-9 (PCSK9) enhances the degradation of hepatic low-density lipoprotein receptor (LDLR). Deletion PCSK9, and loss-of-function mutants in humans result lower levels circulating LDL-cholesterol a strong protection against coronary heart disease. Accordingly, quest for PCSK9 inhibitors has major clinical implications. We have previously identified annexin A2 (AnxA2) as an endogenous binding partner functional inhibitor PCSK9. Herein, we studied relevance...
The MYC oncogene is upregulated in human cancers by translocation, amplification, and mutation of cellular pathways that regulate Myc. Myc/Max heterodimers bind to E box sequences the promoter regions genes activate transcription. inhibitor Omomyc can reduce ability specific promoters target binding directly as demonstrated chromatin immunoprecipitation (CHIP). Here, we demonstrate both a proximity ligation assay (PLA) double (ReCHIP) preferentially binds Max, not Myc, mediate inhibition...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTOrientation of Peptide Fragments from Sos Proteins Bound to the N-Terminal SH3 Domain Grb2 Determined by NMR SpectroscopyMichael Wittekind, Claudio Mapelli, Bennett T. Farmer, II, Ki-Ling Suen, Valentina Goldfarb, Jonglin Tsao, Thomas Lavoie, Mariano Barbacid, Chester A. Meyers, and Luciano MuellerCite this: Biochemistry 1994, 33, 46, 13531–13539Publication Date (Print):November 1, 1994Publication History Published online1 May 2002Published inissue...
Glucagon-like peptide 1 (GLP-1) is a 30 or 31 amino acid hormone that contributes to the physiological regulation of glucose homeostasis and food intake. Herein, we report discovery novel class 11 GLP-1 receptor agonists. These peptides consist structurally optimized 9-mer, which closely related N-terminal 9 acids GLP-1, linked substituted C-terminal biphenylalanine (BIP) dipeptide. SAR studies resulted in 11-mer GLP-1R agonists with similar vitro potency native 30-mer. Peptides 21 22...
Herpes simplex virus type-1 (HSV-1) protease is responsible for proteolytic processing of itself and the assembly protein ICP35 (infected cell 35). Two sites within have recently been identified between Ala247 Ser248 Ala610 Ser611. In this report we demonstrate that peptides corresponding to each these cleavage are substrates recombinant HSV protease-glutathione S-transferase fusion in vitro by high performance liquid chromatography analysis reactions. Analysis products fast atom...
β-APP cleaving enzyme (BACE) is responsible for the first of two proteolytic cleavages APP protein that together lead to generation Alzheimer's disease-associated Aβ peptide. It widely believed halting production peptide, by inhibition BACE, an attractive therapeutic modality treatment disease. BACE aspartyl protease, and there significant effort in pharmaceutical community apply traditional design methods development active site-directed inhibitors this enzyme. We report here discovery a...
Myc, a transcription factor with oncogenic activity, is upregulated by amplification, translocation, and mutation of the cellular pathways that regulate its stability. Inhibition Myc oncogene various modalities has had limited success. One inhibitor, Omomyc, in vivo activity. Here, we report mini‐protein, referred to as Mad, which derived from antagonist Mxd1. Mad localizes nucleus cells 10‐fold more potent than Omomyc inhibiting Myc‐driven cell proliferation. Similar Mxd1, also interacts...
Human cytomegalovirus (HCMV) encodes a protease that cleaves itself and the HCMV assembly protein. Two proteolytic processing sites within were identified at Ala 256–Ser 257 (release site) 643–Ser 644 (maturation site). Identification of rP5‐P4′ mP4‐P6′ as minimal peptide substrates spanning release maturation cleavage sites, respectively, demonstrated requirement for residues flanking conserved core in substrate recognition hydrolysis, which are unique to HCMV. Kinetic parameters determined...
Four diastereomeric D‐Ala 2 ,Leu 5 ‐enkephalins have been synthesized and their CD spectra rat brain binding affinities determined. Only the peptides containing Z‐cyclopropyl phenylalanine residues showed strong affinity. No correlation between bioactivity could be made.
The Myc transcription factor represents an "undruggable" target of high biological interest due to its central role in various cancers. An abbreviated form the c-Myc protein, called Omomyc, consists DNA-binding domain and a coiled-coil region facilitate dimerization 90 amino acid polypeptide. Here we present our results evaluate synthesis Omomyc using three complementary strategies: linear Fmoc solid-phase peptide (SPPS) several advancements for difficult sequences, native chemical ligation...
A series of esters L‐aspartyl‐1‐aminocyclopropane carboxylic acid has been prepared and their sweet tastes determined. The sweetest ester was about 300 times sweeter than sucrose. An attempt to use basic conditions during preparation the dipeptide allyl led succinimide formation aspartyl peptide even though β‐carboxyl group protected by a t‐butyl function. X‐ray structure propyl ( 1c ) determined its conformation is discussed.
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of racemic (E)- and (Z)-2,3-methanotyrosine: new cyclopropane analogs tyrosineClaudio Mapelli, Gregory Turocy, Frank L. Switzer, Charles H. StammerCite this: J. Org. Chem. 1989, 54, 1, 145–149Publication Date (Print):January 1989Publication History Published online1 May 2002Published inissue 1 January 1989https://pubs.acs.org/doi/10.1021/jo00262a033https://doi.org/10.1021/jo00262a033research-articleACS PublicationsRequest reuse...
Abstract A novel thyrotropin‐releasing hormone (TRH) analogue, [2, 4‐MePro 3 ]‐TRH (2, 4‐MePro: 2‐carboxy‐2, 4‐methanopyrrolidine), has been synthesized using a rapid solid phase peptide synthesis method, and its conformational properties investigated by one‐ two‐ dimensional (2D) nmr spectroscopy proton Overhauser measurements. Following published approach, calibrated interproton effects were used together with distance geometry analysis to deduce that the single conformation of His‐2,...
The synthesis of a 16‐residue, stable isotopically labeled peptide is described for use as LC‐MS/MS (Liquid chromatography‐mass spectrometry/mass spectrometry) internal standard in bioanalytical studies. This serves single universal surrogate capable quantifying wide variety immunoglobulin G and Fc‐fusion protein drug candidates animal species used pre‐clinical development An efficient approach this was developed using microwave‐assisted solid phase (SPPS) techniques, which included the...
2,3-Methano-analogues of glutamic and pyroglutamic acid have been synthesized the β-naphthylamide latter is shown to be stable amino peptidase; crystal structure methyl pyroglutamate analogue has determined.
Abstract The effects of replacing L ‐pyroglutamic acid with the cyclopropane analogue 2,3‐methanopyroglutamic (2,3‐MeGlp) on conformation and enzymatic stability have been investigated in 2,3‐MeGlp‐NHMe novel thyrotropin releasing hormone (TRH) [2,3‐MeGlp 1 ]‐TRH by x‐ray diffraction nmr. While adopts a folded (small ψ angle) solid state, several conformations are available to molecule solution. H‐nmr diastereomeric mixture [(±)‐2,3‐MeGlp indicates close orientation pyrrolidone imidazole...