A5022527827- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Chemical Synthesis and Analysis
- Crystallography and molecular interactions
- Synthetic Organic Chemistry Methods
- Synthesis and Catalytic Reactions
- Neuropeptides and Animal Physiology
- Microbial Natural Products and Biosynthesis
- Neonatal Respiratory Health Research
- Mass Spectrometry Techniques and Applications
- Preterm Birth and Chorioamnionitis
- Oxidative Organic Chemistry Reactions
- Click Chemistry and Applications
- Protein Kinase Regulation and GTPase Signaling
- Analytical Chemistry and Chromatography
- Microfluidic and Capillary Electrophoresis Applications
- Receptor Mechanisms and Signaling
- RNA Interference and Gene Delivery
- Machine Learning in Bioinformatics
- Antimicrobial Peptides and Activities
- Asymmetric Synthesis and Catalysis
- Enzyme Catalysis and Immobilization
- Chemical synthesis and alkaloids
- Carbohydrate Chemistry and Synthesis
iCo Therapeutics (Canada)
2024
Université de Montréal
2015-2022
University of British Columbia
2022
An efficient method for synthesizing different functionalized azabicyclo[X.Y.0]alkanone amino acid derivatives has been developed employing electrophilic transannular cyclizations of 8-, 9-, and 10-membered unsaturated macrocycles to form 5,5-, 6,5-, 7,5-, 6,6-fused bicylic acids, respectively. Macrocycles were obtained by a sequence featuring peptide coupling vinyl-, allyl-, homoallyl-, homohomoallylglycine building blocks followed ring-closing metathesis. X-ray crystallographic analyses...
Peptide mimicry employing a combination of aza-amino acyl proline and indolizidinone residues has been used to develop allosteric modulators the prostaglandin F2α receptor. The systematic study N-terminal phenylacetyl moiety conformation side chain functions central turn dipeptide residue demonstrated sensitive relationships between modulator activity topology. Examination aza-Gly-Pro aza-Phe-Pro analogs 2a 2b in murine preterm labor model featuring treatment with lipopolysaccharide their...
Sets of azabicyclo[X.Y.0]alkanone amino acids have been effectively used to identify active conformers in peptide-based drug discovery, but they usually require multiple routes synthesize. Employing a common method from the same nine-membered unsaturated lactam precursor, we developed conditions for stereo- and regiochemical transannular cyclizations synthesize three different indolizidin-2- 9-one acid (I2aa I9aa) analogues. For example, (3S,5R,6R,9S)- (3S,5S,6S,9S)-I2aa diastereomers were...
Azacyclo- and azabicycloalkanone peptidomimetics were synthesized regio- diastereoselectively by iodoacetoxylation transannular amidation reactions on unsaturated lactam precursors contingent ring size, olefin position, solvent, hypervalent iodine(III) reagent. 4-Iodopyrrolizidinone 1, 7-iodoindolizidinone 2, 4-iodo-5-acetoxylactams (e.g., 6 7) made stereospecifically from 7–9-membered olefins 16, iodine, in acetonitrile or toluene, respectively. X-ray crystallography demonstrated potential...
Enantiomerically pure 4-vinylproline (Vyp) was synthesized by a five-step approach from N-(Boc)iodo-alanine (2) featuring copper-catalyzed SN2′ substitution of the corresponding zincate onto (Z)-1,4-dichlorobut-2-ene to prepare methyl 2-N-(Boc)amino-4-(chloromethyl)hexenoate (3). Intra- and intermolecular displacement chloride provided respectively Vyp 2-N-(Boc)amino-4-(azidomethyl)hexenoate (7) suitable for synthesis constrained peptide analogs.
The Claisen self-condensation of lactones can be carried out safely and efficiently under Mukaiyama conditions, in the presence TiCl4 triethylamine. primary products elaborated to various derivatives or converted directly into dihydroxyketones. Such compounds are valuable educts for synthesis ionizable lipids delivery nucleic acid therapeutics now accessed through a concise, economical, scalable route that avoids more technically challenging reaction sequences.
Promiscuous G protein-coupled receptors (GPCRs) engage multiple Gα subtypes with different efficacies to propagate signals in cells. A mechanistic understanding of selectivity by GPCRs is critical for therapeutic design, since signaling can be restrained ligand-receptor complexes preferentially specific proteins. However, details GPCR are unresolved. Here, we investigated cognate protein using the prototypical promiscuous Gαq/11 and Gα12/13 coupling receptors, angiotensin II type I receptor...