More Like this

1. Advancing Glycan Analysis: A New Platform Integrating SERS, Boronic Acids, and Machine Learning Algorithms

   https://doi.org/10.1002/adsr.202300052  

   Hu, Qiang; Kuai, Dacheng; Park, Hyundo; Clark, Haley; Balbuena, Perla_B; Kwon, Joseph_Sang‐Il; Wu, Hung‐Jen (June 2023, Advanced Sensor Research)

   Abstract Glycans are the most abundant fundamental biomolecules, but profiling glycans is challenging due to their structural complexity. To address this, a novel glycan detection platform is developed by integrating surface‐enhanced Raman spectroscopy (SERS), boronic acid receptors, and machine learning tools. Boronic acid receptors bind with glycans, and the reaction influences molecular vibrations, leading to unique Raman spectral patterns. Unlike prior studies that focus on designing a boronic acid with high binding selectivity toward a target glycan, this sensor is designed to analyze overall changes in spectral patterns using machine learning algorithms. For proof‐of‐concept, 4‐mercaptophenylboronic acid (4MBA) and 1‐thianthrenylboronic acid (1TBA) are used for glycan detection. The sensing platform successfully recognizes the stereoisomers and the structural isomers with different glycosidic linkages. The collective spectra that combine the spectra from both boronic acid receptors improve the performance of the support vector machine model due to the enrichment of the structural information of glycans. In addition, this new sensor could quantify the mole fraction of sialic acid in lactose background using the machine learning regression technique. This low‐cost, rapid, and highly accessible sensor will provide the scientific community with another option for frequent comparative glycan screening in standard biological laboratories. 

   more » « less
2. Synthesis of Dihydropyrazoles via Palladium‐Catalyzed Cascade Heterocyclization/Carbonylation/Arylation of β,γ‐Unsaturated N ‐Tosyl Hydrazones

   https://doi.org/10.1002/adsc.202301326  

   Dantas, Juliana_A; Hardy, Melissa_A; Costa, Mateus_O; De_Oliveira, Camila_P; Cabral, Tadeu_L_G; Tormena, Claudio_Francisco; Sigman, Matthew_S; Ferreira, Marco_A_B (December 2023, Advanced Synthesis & Catalysis)

   Abstract A Pd‐catalyzed heterocyclization/carbonylation/arylation cascade reaction between β,γ‐unsaturated N−Ts hydrazones and commercially available arylboronic acids as coupling partners is described, producing 2‐pyrazoline‐ketone derivatives in 11–78% yield. A detailed statistical analysis of reactivity patterns of boronic acids provided key information about the limitations of the method, highlighting the challenges of degradation pathways. Our methodology offers a tool for synthesizing diverse 2‐pyrazoline‐ketone derivatives, expanding the toolbox of accessible N−N‐heterocycles. 

   more » « less
3. Copper-mediated peptide arylation selective for the N-terminus

   https://doi.org/10.1039/D0SC02933E  

   Miller, Mary K.; Wang, Haopei; Hanaya, Kengo; Zhang, Olivia; Berlaga, Alex; Ball, Zachary T. (October 2020, Chemical Science)

   null (Ed.)

   Polypeptides present remarkable selectivity challenges for chemical methods. Amino groups are ubiquitous in polypeptide structure, yet few paradigms exist for reactivity and selectivity in arylation of amine groups. This communication describes the utilization of boronic acid reagents bearing certain o -electron withdrawing groups for copper-mediated amine arylation of the N-terminus under mild conditions and primarily aqueous solvent. The method adds to the toolkit of boronic acid reagents for polypeptide modification under mild conditions in water that shows complete selectivity for the N-terminus in the presence of lysine side chains. 

   more » « less
4. Boronic Acid Reagents for Transition‐Metal‐Mediated Cross‐Coupling with Proteins and Peptides

   https://doi.org/10.1002/ijch.202100012  

   Miller, Mary K.; Ball, Zachary T. (April 2021, Israel Journal of Chemistry)

   Abstract Transition‐metal catalysis provides new approaches to selectivity and the activation of otherwise inert functional groups. Bioconjugation with protein and peptide substrates presents numerous challenges of functional group activation and selectivity, and transitional‐metal approaches provide important alternative solutions to these challenges. This article describes the development of boronic acid reagents for new selective approaches to modification of peptides and proteins, focusing primarily on catalytic C−X bond formation. 

   more » « less
5. Diastereoselective Synthesis of (3R,5R)-γ-Hydroxypiperazic Acid

   https://doi.org/10.1055/s-0040-1719824  

   Gerrein, Taylor A.; Elbatrawi, Yassin M.; Del Valle, Juan R. (October 2021, Synlett)

   Abstract We report an asymmetric synthesis of the (3R,5R)-γ-hydroxypiperazic acid (γ-OHPiz) residue encountered in several bioactive nonribosomal peptides. Our strategy relies on a diastereoselective enolate hydroxylation reaction and electrophilic N-amination to provide the acyclic γ-OHPiz precursor. This orthogonally protected α-hydrazino acid intermediate is amenable to late-stage diazinane ring formation following incorporation into a peptide chain. We determined the N-terminal amide rotamer propensity of the γ-OHPiz residue and showed that the γ-OH substituent enhances trans-amide bias relative to piperazic acid. 

   more » « less