Read by QxMD icon Read

Constrained peptide

Kenneth E Schwieter, Jeffrey N Johnston
Peptide synthesis is a truly interdisciplinary tool, familiar to a broad group of scientists who do not otherwise overlap scientifically. For this reason, some may perceive even complex peptide synthesis to be a "solved problem", while others might argue that immense opportunity remains untapped or simply inaccessible. At the extreme of complexity, what might a concise assessment of the state-of-the-art in peptide synthesis look like? As one of the most practiced forms of synthetic chemistry by chemists and non-chemists alike, what restrictions remain that constrain access to chemical space? Using popular terminology, what forms of peptide synthesis are appropriately termed "on-demand"? The purpose of this Perspective is to appraise synthetic access to complex peptides, particularly those containing unnatural α-amino amides...
October 14, 2016: Journal of the American Chemical Society
Carmen Burtea, Sophie Laurent, Tuba Sanli, Deborah Fanfone, Aude Devalckeneer, Sébastien Sauvage, Marie-Claire Beckers, Sandrine Rorive, Isabelle Salmon, Luce Vander Elst, Bernard R Lauwerys, Robert N Muller
BACKGROUND: Interleukin-7 receptor alpha (IL-7Rα) represents a biomarker with potential applications in rheumatoid arthritis (RA) diagnosis and therapy. We have therefore searched by phage display potential IL-7Rα specific peptides with the primary goal being to develop in vivo molecular imaging tools. METHODS: IL-7Rα-targeted peptides were searched within a disulfide-constrained combinatorial phage displayed library of random linear heptapeptides. The apparent dissociation constant (Kd) and half maximal inhibition constant (IC50) were estimated for phage clones and synthesized peptides by ELISA...
October 12, 2016: Arthritis Research & Therapy
Kelly L Keeling, Okki Cho, Denis B Scanlon, Grant W Booker, Andrew D Abell, Kate L Wegener
Constrained α-helical peptides are showing potential as biological probes and therapeutic agents that target protein-protein interactions. However, the factors that determine the optimal constraint locations are still largely unknown. Using the β-integrin/talin protein interaction as a model system, we examine the effect of constraint location on helical conformation, as well as binding affinity, using circular dichroism and NMR spectroscopy. Stapling increased the overall helical content of each integrin-based peptide tested...
October 18, 2016: Organic & Biomolecular Chemistry
Yuksel Batir, Thaddeus A Bargiello, Terry L Dowd
In this article we present (1)H and (13)C chemical shift assignments, secondary structural propensity data and normalized temperature coefficient data for N-terminal peptides of Connexin 26 (Cx26), Cx26G12R and Cx32G12R mutants seen in syndromic deafness and Charcot Marie Tooth Disease respectively, published in "Structural Studies of N-Terminal Mutants of Connexin 26 and Connexin 32 Using 1H NMR Spectroscopy" (Y. Batir, T.A. Bargiello, T.L. Dowd, 2016) [1]. The mutation G12R affects the structure of both Cx26 and Cx32 peptides differently...
December 2016: Data in Brief
Nina Bionda, Rudi Fasan
Many biologically active peptides found in nature exhibit a bicyclic structure wherein a head-to-tail cyclic backbone is further constrained by an intramolecular linkage connecting two side chains of the peptide. Accordingly, methods to access macrocyclic peptides sharing this overall topology could be of significant value toward the discovery of new functional entities and bioactive compounds. With this goal in mind, we recently developed a strategy for enabling the biosynthesis of thioether-bridged bicyclic peptides in living bacterial cells...
2017: Methods in Molecular Biology
Alysha G Elliott, Bastian Franke, David A Armstrong, David J Craik, Joshua S Mylne, K Johan Rosengren
We recently isolated and described the evolutionary origin of a diverse class of small single-disulfide bonded peptides derived from Preproalbumin with SFTI-1 (PawS1) proteins in the seeds of flowering plants (Asteraceae). The founding member of the PawS derived peptide (PDP) family is the potent trypsin inhibitor SFTI-1 (sunflower trypsin inhibitor-1) from Helianthus annuus, the common sunflower. Here we provide additional structures and describe the structural diversity of this new class of small peptides, derived from solution NMR studies, in detail...
October 1, 2016: Amino Acids
Olivier Van der Poorten, Astrid Knuhtsen, Daniel Sejer Pedersen, Steven Ballet, Dirk Tourwé
Constraining the conformation of flexible peptides is a proven strategy to increase potency, selectivity and metabolic stability. The focus has mostly been on constraining the backbone dihedral angles; however, the correct orientation of the amino acid side chains (Χ-space) which constitute the peptide pharmacophore is equally important. Control of Χ-space utilizes conformationally constrained amino acids which favor, disfavor or exclude the gauche (‒), the gauche (+) or the trans conformation. In this review we focus on cyclic aromatic amino acids in which the side chain is connected to the peptide backbone to provide control of Χ1- and Χ2-space...
October 3, 2016: Journal of Medicinal Chemistry
Gaurav Bhardwaj, Vikram Khipple Mulligan, Christopher D Bahl, Jason M Gilmore, Peta J Harvey, Olivier Cheneval, Garry W Buchko, Surya V S R K Pulavarti, Quentin Kaas, Alexander Eletsky, Po-Ssu Huang, William A Johnsen, Per Jr Greisen, Gabriel J Rocklin, Yifan Song, Thomas W Linsky, Andrew Watkins, Stephen A Rettie, Xianzhong Xu, Lauren P Carter, Richard Bonneau, James M Olson, Evangelos Coutsias, Colin E Correnti, Thomas Szyperski, David J Craik, David Baker
Naturally occurring, pharmacologically active peptides constrained with covalent crosslinks generally have shapes that have evolved to fit precisely into binding pockets on their targets. Such peptides can have excellent pharmaceutical properties, combining the stability and tissue penetration of small-molecule drugs with the specificity of much larger protein therapeutics. The ability to design constrained peptides with precisely specified tertiary structures would enable the design of shape-complementary inhibitors of arbitrary targets...
September 14, 2016: Nature
Eva Schütznerová, Pedro Verdía, Viktor Krchňák
3,4,4a,5-Tetrahydrobenzo[e]pyrazino[2,1-c][1,2,4]thiadiazin-1(2H)-one 6,6-dioxides, molecular scaffolds with 3D architecture, were synthesized on solid supports via tandem N-acyl iminium ion cyclization followed by nucleophilic addition. The modular synthesis proceeded under mild conditions using commercially available building blocks and provided crude products with respectable purity. The synthesized compounds are applicable as fused nitrogenous heterocyclic compounds in drug discovery and as constrained peptidomimetics incorporated into a peptide backbone...
October 10, 2016: ACS Combinatorial Science
Olivier M F Martin, Loïc Etheve, Guillaume Launay, Juliette Martin
Terminal residues of protein chains are charged and more flexible than other residues since they are constrained only on one side. Do they play a particular role in protein-protein and protein-DNA interfaces? To answer this question, we considered large sets of non-redundant protein-protein and protein-DNA complexes and analyzed the status of terminal residues and their involvement in interfaces. In protein-protein complexes, we found that more than half of terminal residues (62%) are either modified by attachment of a tag peptide (10%) or have missing coordinates in the analyzed structures (52%)...
2016: PloS One
Eivind A B Undheim, Ronald A Jenner, Glenn F King
INTRODUCTION: Centipedes are one of the oldest and most successful lineages of venomous terrestrial predators. Despite their use for centuries in traditional medicine, centipede venoms remain poorly studied. However, recent work indicates that centipede venoms are highly complex chemical arsenals that are rich in disulfide-constrained peptides that have novel pharmacology and three-dimensional structure. AREAS COVERED: This review summarizes what is currently known about centipede venom proteins, with a focus on disulfide-rich peptides that have novel or unexpected pharmacology that might be useful from a therapeutic perspective...
September 9, 2016: Expert Opinion on Drug Discovery
Philipp M Cromm, Kerstin Wallraven, Adrian Glas, David Bier, Alois Fürstner, Christian Ottmann, Tom N Grossmann
Macrocyclization can be used to constrain peptides in their bioactive conformations, thereby supporting target affinity and bioactivity. In particular, for the targeting of challenging protein-protein interactions, macrocyclic peptides have proven to be very useful. Available approaches focus on the stabilization of α-helices, which limits their general applicability. Here we report for the first time on the use of ring-closing alkyne metathesis for the stabilization of an irregular peptide secondary structure...
September 6, 2016: Chembiochem: a European Journal of Chemical Biology
L Peraro, T R Siegert, J A Kritzer
Macrocyclic peptides are highly promising as inhibitors of protein-protein interactions. While many bond-forming reactions can be used to make cyclic peptides, most have limitations that make this chemical space challenging to access. Recently, a variety of cysteine alkylation reactions have been used in rational design and library approaches for cyclic peptide discovery and development. We and others have found that this chemistry is versatile and robust enough to produce a large variety of conformationally constrained cyclic peptides...
2016: Methods in Enzymology
Saleh Umair, Qing Deng, Joanna M Roberts, Richard J Shaw, Ian A Sutherland, Anton Pernthaner
Phage display was used to identify peptide mimics of an immunologically protective nematode glycan (CarLA) by screening a constrained C7C peptide library for ligands that bound to an anti-CarLA mAb (PAB1). Characterisation of these peptide mimotopes revealed functional similarities with an epitope that is defined by PAB1. Mimotope vaccinations of mice with three selected individual phage clones facilitated the induction of antibody responses that recognised the purified, native CarLA molecule which was obtained from Trichostrongylus colubriformis...
2016: PloS One
Minying Cai, Victor J Hruby
This paper describes the development of cyclic peptides for G protein coupled receptors to enable structure-function knowledge and the design of novel therapeutics. One important property of cyclic peptides is that they tend to be resistant to the digestion, enabling them to survive in the human digestive tract. This trait makes them very important as drug leads or as scaffolds which, in theory, can be engineered to incorporate a peptide domain of medicinal value. This is especially important for delivery of peptides that would be destroyed without such implementation...
August 25, 2016: Biopolymers
Shiri Yacobovich, Lena Tuchinsky, Michael Kirby, Tetiana Kardash, Oryan Agranyoni, Elimelech Nesher, Boris Redko, Gary Gellerman, Dror Tobi, Katerina Gurova, Igor Koman, Osnat Ashur Fabian, Albert Pinhasov
ALOS4, a unique synthetic cyclic peptide without resemblance to known integrin ligand sequences, was discovered through repeated biopanning with pIII phage expressing a disulfide-constrained nonapeptide library. Binding assays using a FITC-labeled analogue demonstrated selective binding to immobilized αvβ3 and a lack of significant binding to other common proteins, such as bovine serum albumin and collagen. In B16F10 cell cultures, ALOS4 treatment at 72 h inhibited cell migration (30%) and adhesion (up to 67%)...
August 18, 2016: Oncotarget
Q Liu, H Zhao, Y Jiang, M Wu, Y Tian, D Wang, Y Lao, N Xu, Z Li
Despite great advances in cancer therapy, drug resistance is a difficult hurdle to overcome that requires development of anticancer agents with novel and effective modes of action. In a number of studies, lytic peptides have shown remarkable ability to eliminate cancer cells through a different way from traditional treatments. Lytic peptides are positively charged, amphiphilic, and are efficient at binding and disrupting the negatively charged cell membrane of cancer cells. In this study, we described the anticancer properties of a lytic peptide that was developed on the basis of the alignment of amphiphilic BH3 peptides...
2016: Cell Death Discovery
Basavalingappa Vasantha, Gijo George, Srinivasarao Raghothama, Padmanabhan Balaram
Novel helical, structures unprecedented in the chemistry of α-polypeptides, may be found in polypeptides containing β and γ amino acids. The structural characterization of C12 and C14 -helices in oligo β-peptides was originally achieved using conformationally constrained cyclic β-residues. This study explores the conformational characteristics of proteinogenic β(3) residues in homooligomeric sequences and addresses the issue of inducing a transition between C14 and C12 helices by the introduction of a guest α-residue...
August 19, 2016: Biopolymers
Brian F Fisher, Samuel H Gellman
α/γ-Peptide foldamers containing either γ(4)-amino acid residues or ring-constrained γ-amino acid residues have been reported to adopt 12-helical secondary structure in nonpolar solvents and in the solid state. These observations have engendered speculation that the seemingly flexible γ(4) residues have a high intrinsic helical propensity and that residue-based preorganization may not significantly stabilize the 12-helical conformation. However, the prior studies were conducted in environments that favor intramolecular H-bond formation...
August 31, 2016: Journal of the American Chemical Society
Astrid Knuhtsen, Baptiste Legrand, Olivier Van der Poorten, Muriel Amblard, Jean Martinez, Steven Ballet, Jesper L Kristensen, Daniel Sejer Pedersen
Protein arginine N-methyl transferases (PRMTs) belong to a family of enzymes that modulate the epigenetic code through modifications of histones. In the present study, peptides emerging from a phage display screening were modified in the search for PRMT inhibitors through substitution with non-proteinogenic amino acids, N-alkylation of the peptide backbone, and incorporation of constrained dipeptide mimics. One of the modified peptides (23) showed an increased inhibitory activity towards several PRMTs in the low μm range and the conformational preference of this peptide was investigated and compared with the original hit using circular dichroism and NMR spectroscopy...
September 19, 2016: Chemistry: a European Journal
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"