A single chiral cyclic α,α-disubstituted amino acid, (3S,4S)-1-amino-(3,4-dimethoxy)cyclopentanecarboxylic acid [(S,S)-Ac(5)c(dOM)], was placed at the N-terminal or C-terminal positions of achiral α-aminoisobutyric acid (Aib) peptide segments. The IR and (1)H NMR spectra indicated that the dominant conformations of two peptides Cbz-[(S,S)-Ac(5)c(dOM)]-(Aib)(4)-OEt (1) and Cbz-(Aib)(4)-[(S,S)-Ac(5)c(dOM)]-OMe (2) in solution were helical structures. X-ray crystallographic analysis of 1 and 2 revealed that a left-handed (M) 3(10)-helical structure was present in 1 and that a right-handed (P) 3(10)-helical structure was present in 2 in their crystalline states.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1002/psc.1273 | DOI Listing |
Nat Commun
January 2025
Department of Molecular Biosciences, University of South Florida, 4202 E Fowler Ave, Tampa, FL, 33620, USA.
Unraveling the signaling roles of intermediate complexes is pivotal for G protein-coupled receptor (GPCR) drug development. Despite hundreds of GPCR-Gαβγ structures, these snapshots primarily capture the fully activated complex. Consequently, the functions of intermediate GPCR-G protein complexes remain elusive.
View Article and Find Full Text PDFSci Signal
January 2025
Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
The small GTPase R-RAS2 regulates homeostatic proliferation and survival of T and B lymphocytes and, when present in high amounts, drives the development of B cell chronic lymphocytic leukemia. In normal and leukemic lymphocytes, R-RAS2 constitutively binds to antigen receptors through their immunoreceptor tyrosine-based activation motifs (ITAMs) and promotes tonic activation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway. Here, we examined the molecular mechanisms underlying this direct interaction and its consequences for R-RAS2 activity.
View Article and Find Full Text PDFAcc Chem Res
January 2025
Molecular Sensing and Imaging Center, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China.
ConspectusIons are the crucial signaling components for living organisms. In cells, their transportation across pore-forming membrane proteins is vital for regulating physiological functions, such as generating ionic current signals in response to target molecule recognition. This ion transport is affected by confined interactions and local environments within the protein pore.
View Article and Find Full Text PDFAsian Pac J Cancer Prev
January 2025
Parul Institute of Applied Sciences, Parul University, Vadodara, India.
Background: Breast cancer remains a significant global health challenge, requiring innovative therapeutic strategies. In silico methods, which leverage computational tools, offer a promising pathway for vaccine development. These methods facilitate antigen identification, epitope prediction, immune response modelling, and vaccine optimization, accelerating the design process.
View Article and Find Full Text PDFBiochemistry
January 2025
Department of Biochemistry, Genetics and Microbiology, Faculty of Natural and Agricultural Sciences, University of Pretoria, Pretoria 0002, South Africa.
C-terminal amidation of antimicrobial peptides (AMPs) is a frequent minor modification used to improve antibacterial potency, commonly ascribed to increased positive charge, protection from proteases, and a stabilized secondary structure. Although the activity of AMPs is primarily associated with the ability to penetrate bacterial membranes, hitherto the effect of amidation on this interaction has not been understood in detail. Here, we show that amidation of the scorpion-derived membranolytic peptide AamAP1-Lys produces a potent analog with faster bactericidal activity, increased membrane permeabilization, and greater Gram-negative membrane penetration associated with greater conformational flexibility.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!