More Like this

1. Secondary amine selective Petasis (SASP) bioconjugation

   https://doi.org/10.1039/C9SC04697F  

   Sim, Yonnette E.; Nwajiobi, Ogonna; Mahesh, Sriram; Cohen, Ryan D.; Reibarkh, Mikhail Y.; Raj, Monika (January 2020, Chemical Science)

   Selective modification of proteins enables synthesis of antibody-drug conjugates, cellular drug delivery and construction of new materials. Many groups have developed methods for selective N-terminal modification without affecting the side chain of lysine by judicious pH control. This is due to lower basicity of the N-terminus relative to lysine side chains. But none of the methods are capable of selective modification of secondary amines or N-terminal proline, which has similar basicity as lysine. Here, we report a secondary amine selective Petasis (SASP) reaction for selective bioconjugation at N-terminal proline. We exploited the ability of secondary amines to form highly electrophilic iminium ions with aldehydes, which rapidly reacted with nucleophilic organoboronates, resulting in robust labeling of N-terminal proline under biocompatible conditions. This is the first time the Petasis reaction has been utilized for selective modification of secondary amines on completely unprotected peptides and proteins under physiological conditions. Peptide screening results showed that the reaction is highly selective for N-terminal proline. There are no other chemical methods reported in literature that are selective for N-terminal proline in both peptides and proteins. This is a multicomponent reaction leading to the synthesis of doubly functionalized bioconjugates in one step that can be difficult to achieve using other methods. The key advantage of the SASP reaction includes its high chemoselective and stereoselective (>99% de) nature, and it affords dual labeled proteins in one pot. The broad utility of this bioconjugation is highlighted for a variety of peptides and proteins, including aldolase and creatine kinase. 

   more » « less
2. Dehydrogenases in the Flavoprotein Amine Oxidoreductase Superfamily

   https://doi.org/10.1021/acs.biochem.5c00129  

   Akram, Javeria; Budagavi, Tavishi; Zhang, Zhiyao; Fowler, Morgan; Gaunt, Andrew_J; Barkman, Todd_J; Stull, Frederick (June 2025, Biochemistry)
3. Acridine photocatalysis enables tricomponent direct decarboxylative amine construction

   https://doi.org/10.1039/D4SC02356K  

   Sui, Xianwei; Dang, Hang T; Porey, Arka; Trevino, Ramon; Das, Arko; Fremin, Seth O; Hughes, William B; Thompson, William T; Dhakal, Shree Krishna; Arman, Hadi D; et al (January 2024, Chemical Science)

   Diverse amines and amino acids are now readily accessed from carboxylic acids, aldehydes, and amine precursors in a direct decarboxylative reaction enabled by a homogeneous triple catalytic system based on acridine photocatalysis. 

   more » « less
4. Amine-directed Mizoroki–Heck arylation of free allylamines

   https://doi.org/10.1039/D2QO00041E  

   Landge, Vinod G.; Bonds, Audrey L.; Mncwango, Thandazile A.; Mather, Carolina B.; Saleh, Yasaman; Fields, Hunter L.; Lee, Frank; Young, Michael C. (March 2022, Organic Chemistry Frontiers)

   The transition metal-catalyzed Mizoroki–Heck reaction is a powerful method to synthesize C–C bonds, allowing access to several important pharmaceuticals. Traditionally free amines have not been compatible with these approaches due to oxidation of the amine by the transition metal or other side reactions. However, the functionalization of unprotected allylamines is particularly attractive due to their prevalence in various biologically active molecules. Herein we report the palladium-catalyzed selective monoarylation of free allylamines using aryl iodides. The strategy works on primary, secondary, and tertiary amines, making it very general. Our monoarylation method is scalable and works on aryl iodides with a variety of substituted arene or heterocycle motifs, including chromophoric substrates. 

   more » « less
5. Growth and transcriptional response of wheat and rice to the tertiary amine BMVE

   https://doi.org/10.3389/fpls.2023.1273620  

   Dharni, Jaspinder Singh; Shi, Yu; Zhang, Chi; Petersen, Chris; Walia, Harkamal; Staswick, Paul (January 2024, Frontiers in Plant Science)

   IntroductionSeed vigor is largely a product of sound seed development, maturation processes, genetics, and storage conditions. It is a crucial factor impacting plant growth and crop yield and is negatively affected by unfavorable environmental conditions, which can include drought and heat as well as cold wet conditions. The latter leads to slow germination and increased seedling susceptibility to pathogens. Prior research has shown that a class of plant growth regulators called substituted tertiary amines (STAs) can enhance seed germination, seedling growth, and crop productivity. However, inconsistent benefits have limited STA adoption on a commercial scale MethodsWe developed a novel seed treatment protocol to evaluate the efficacy of 2-(N-methyl benzyl aminoethyl)-3-methyl butanoate (BMVE), which has shown promise as a crop seed treatment in field trials. Transcriptomic analysis of rice seedlings 24 h after BMVE treatment was done to identify the molecular basis for the improved seedling growth. The impact of BMVE on seed development was also evaluated by spraying rice panicles shortly after flower fertilization and subsequently monitoring the impact on seed traits. ResultsBMVE treatment of seeds 24 h after imbibition consistently improved wheat and rice seedling shoot and root growth in lab conditions. Treated wheat seedlings grown to maturity in a greenhouse also resulted in higher biomass than controls, though only under drought conditions. Treated seedlings had increased levels of transcripts involved in reactive oxygen species scavenging and auxin and gibberellic acid signaling. Conversely, several genes associated with increased reactive oxygen species/ROS load, abiotic stress responses, and germination hindering processes were reduced. BMVE spray increased both fresh and mature seed weights relative to the control for plants exposed to 96 h of heat stress. BMVE treatment during seed development also benefited germination and seedling growth in the next generation, under both ambient and heat stress conditions. DiscussionThe optimized experimental conditions we developed provide convincing evidence that BMVE does indeed have efficacy in plant growth enhancement. The results advance our understanding of how STAs work at the molecular level and provide insights for their practical application to improve crop growth. 

   more » « less