116821-47-7Relevant articles and documents
Syntheses and transglutaminase-catalyzed incorporation of novel spin-labeled primary amines into proteins
Narasimhan, Chakravarthy,Lai, Ching-San,Joseph, Joy
, p. 50 - 58 (1996)
A series of spin-labeled primary amine derivatives, namely, 2,2,6,6-tetramethyl-piperidinyl-oxyl-4-amidoalkylamines with varying alkyl chain lengths, have been synthesized. The spin-labeled primary amine-with a tetramethylene or a pentamethylene chain covalently modifies human plasma fibronectin with a stoichiometry of 0.97-to-1.0 (probe-to-subunit) in the presence of coagulation factor XIIIa. The labels with two or one methylene chain also similarly modify fibronectin, but with a stoichiometry of only about 0.3-0.4 per subunit. The spin-labeled primary amine with a trimethylene chain does not label fibronectin. The labeling site appears to be the glutamine-3 residue at the amino-terminal region of fibronectin. Electron spin resonance studies show that the bound labels are partially immobilized with an effective rotational correlation time of 0.4-0.6 ns. The spin-labeled primary amine with tetramethylene chain also is shown to covalently incorporate into bee venom melittin in the presence of guinea-pig liver transglutaminase. The syntheses of the various spin-labeled primary amines and their applications in the study of structure and dynamics of different proteins and peptides are discussed. The observations from this study suggest that these spin-labeled primary amines have potentially wide application as structural probes.
Improving the Specificity of the Prostate-Specific Antigen Substrate Glutaryl-Hyp-Ala-Ser-Chg-Gln as a Promoiety
Aloysius, Herve,Hu, Longqin
, p. 837 - 848 (2015)
To develop PSA peptide substrates with improved specificity and plasma stability from the known substrate sequence glutaryl-Hyp-Ala-Ser-Chg-Gln, systematic replacements of the N-terminal segment with D-retro-inverso-peptides were performed with the incorporation of 7-amino-4-methylcoumarin (7-AMC) after Gln for convenient fluorometric determination and ranking of the PSA substrate activity. The D-retro-inverso-peptide conjugates with P2-P5 D-amino acid substitutions were moderate but poorer PSA substrates as compared to the original peptide, suggesting that inversion of the amide bonds and/or incorporation of the additional atom as in the urea linker adversely affected PSA binding. However, P5 substitution of Hyp with Ser showed significant improvements in PSA cleavage rate; the resulting AMC conjugate, glutaryl-Ser-Ala-Ser-Chg-Gln-AMC (11), exhibited the fastest PSA cleavage rate of 351 pmol/min/100 nmol PSA. In addition, GABA←mGly-Ala-Ser-Chg-Gln-AMC (conjugate 6) was the second best PSA substrate and released 7-AMC at a rate of 225 pmol/min/100 nmol PSA as compared to 171 pmol/min/100 nmol PSA for the control conjugate glutaryl-Hyp-Ala-Ser-Chg-Gln-AMC. Incubations of selected AMC conjugates with mouse and human plasma revealed that GABA←D-Ser-ψ[NH-CO-NH]-Ala-Ser-Chg-Gln-AMC (5) and GABA←mGly-Ala-Ser-Chg-Gln-AMC (6) were most stable to non-PSA-mediated proteolysis. Our results suggest that the PSA specificity of glutaryl-Hyp-Ala-Ser-Chg-Gln is improved with Ser and mGly substitutions of Hyp at the P5.
Enzymatic removal of carboxyl protecting groups. 1. Cleavage of the tert-butyl moiety
Schmidt, Marlen,Barbayianni, Efrosini,Fotakopoulou, Irene,Hoehne, Matthias,Constantinou-Kokotou, Violetta,Bornscheuer, Uwe T.,Kokotos, George
, p. 3737 - 3740 (2005)
(Chemical Equation Presented) A recent discovery that a certain amino acid motif (GGG-(A)X-motif) in lipases and esterases determines their activity toward tertiary alcohols prompted us to investigate the use of these biocatalysts in the mild and selective removal of tert-butyl protecting groups in amino acid derivatives and related compounds. An esterase from Bacillus subtilis (BsubpNBE) and lipase A from Candida antarctica (CAL-A) were identified as the most active enzymes, which hydrolyzed a range of tert-butyl esters of protected amino acids (e.g., Boc-Tyr-OtBu, Z-GABA-OtBu, Fmoc-GABA-O tBu) in good to high yields and left Boc, Z, and Fmoc-protecting groups intact.
DNA-binding ligands from peptide libraries containing unnatural amino acids
Lescrinier, Theo,Hendrix, Chris,Kerremans, Luc,Rozenski, Jef,Link, Andreas,Samyn, Bart,Van Aerschot, Arthur,Lescrinier, Eveline,Eritja, Ramon,Van Beeumen, Jozef,Herdewijn, Piet
, p. 425 - 433 (1998)
An unnatural peptide-based library, bound on a solid support, was screened for double-stranded-DNA (dsDNA)-binding ligands. For this purpose, fluorescein and rhodamine were used to label the single-stranded oigodeoxynucleotides. Beads containing products with affinity to dsDNA turned red in visible light and fluoresced yellow in UV light. A similar technique can be used for the selection of ligands which bind to a hairpin RNA, using a monolabelled oligoribonucleotide. The screening process revealed a high structure-affinity relationship in the successful products. Only six out of the twelve unnatural amino acids were selected, with the repeated appearance of AlaU, Sar and the secondary amino acids (Hyp, Inp). The affinity and selectivity for the target was determined using a DNase I protection assay.
4-Methyltrityl-Protected Pyrrole and Imidazole Building Blocks for Solid Phase Synthesis of DNA-Binding Polyamides
Heinrich, Benedikt,Vázquez, Olalla
, p. 533 - 536 (2020)
DNA-binding polyamides are synthetic oligomers of pyrrole/imidazole units with high specificity and affinity for double-stranded DNA. To increase their synthetic diversity, we report a mild methodology based on 4-methyltrityl (Mtt) solid phase peptide synthesis (SPPS), whose building blocks are more accessible than the standard Fmoc and Boc SPPS ones. We demonstrate the robustness of the approach by preparing and studying a hairpin with all precursors. Importantly, our strategy is orthogonal and compatible with sensitive molecules and could be readily automated.
Hydroxamic Acids Immobilized on Resins (HAIRs): Synthesis of Dual-Targeting HDAC Inhibitors and HDAC Degraders (PROTACs)
Bandolik, Jan J.,Bhatia, Sanil,Borkhardt, Arndt,Hamacher, Alexandra,Hansen, Finn K.,Kassack, Matthias U.,Meiler, Jens,Roatsch, Martin,S?nnichsen, Melf,Sch?ler, Andrea,Schoeder, Clara T.,Sinatra, Laura
supporting information, p. 22494 - 22499 (2020/10/12)
Inhibition of more than one cancer-related pathway by multi-target agents is an emerging approach in modern anticancer drug discovery. Here, based on the well-established synergy between histone deacetylase inhibitors (HDACi) and alkylating agents, we present the discovery of a series of alkylating HDACi using a pharmacophore-linking strategy. For the parallel synthesis of the target compounds, we developed an efficient solid-phase-supported protocol using hydroxamic acids immobilized on resins (HAIRs) as stable and versatile building blocks for the preparation of functionalized HDACi. The most promising compound, 3 n, was significantly more active in apoptosis induction, activation of caspase 3/7, and formation of DNA damage (γ-H2AX) than the sum of the activities of either active principle alone. Furthermore, to demonstrate the utility of our preloaded resins, the HAIR approach was successfully extended to the synthesis of a proof-of-concept proteolysis-targeting chimera (PROTAC), which efficiently degrades histone deacetylases.
Dicyclohexylurea derivatives of amino acids as dye absorbent organogels and anion sensors
Roy, Karabi,Ghosh, Suvankar,Chetia, Monikha,Satpati, Priyadarshi,Chatterjee, Sunanda
, p. 3026 - 3039 (2019/03/21)
Dicyclohexyl urea (DCU) derivatives of amino acids Fmoc-Phe-DCU (M1), Fmoc-Phg-DCU (M2) and Fmoc-Gaba-DCU (M3) have been shown to form phase selective, thermoreversible and mechanically robust gels in a large range of organic solvents. This is the first report of low molecular weight gelators (LMWG) from DCU derivatives of amino acids. The self-assembly mechanism of the organogels has been probed using concentration dependent 1H NMR, DMSO titration 1H NMR, fluorescence, FTIR, PXRD and FESEM techniques. Self-assembly leading to gelation process is mainly driven by hydrophobicity and π-π stacking interactions in between Fmoc groups. Interestingly, the gels can absorb several kinds of organic dyes efficiently and can be reused for dye absorption for multiple cycles. Additionally, M1-M3 act as sensors for anions like fluoride, acetate and hydroxide, for which they have specific fluorescence response. Gel formation by M1-M3 is completely arrested in the presence of fluoride. The possible binding mode of fluoride has been delineated using DFT studies. Calculations suggest, involvement of urea NH in a six membered intramolecular hydrogen bond, rendering it unavailable for fluoride binding. Backbone -NH of the amino acids of M1-M3 is responsible for fluoride binding. The reported small, economically viable, synthetically facile molecules not only enrich the repertoire of LMWG molecules, but can have multifaceted applications.
NEW PEPTIDE-LINKED ESTER PRODRUGS ACTIVATED BY PROSTATE-SPECIFIC ANTIGEN
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Paragraph 64-65, (2018/08/26)
The present disclosure is directed to a series of target-selective chemotherapeutic ester prodrugs comprising PSA-cleavable peptides that promote the delivery of free doxorubicin and other chemotherapeutic agents into the prostate and/or prostate tumors with greater efficiency.
SANTACRUZAMATE A COMPOSITIONS AND ANALOGS AND METHODS OF USE
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Page/Page column 44, (2014/02/16)
The compositions and methods described herein relate generally to Santacruzamate A compositions and analogs, which, among other features, are useful as histone deacetylase (HDAC) inhibitors.
Basic techniques of working on a solid phase: From ABC of the peptide synthesis to libraries of non-natural amino acids
Babaev,Ermolat'ev
experimental part, p. 2572 - 2589 (2011/04/15)
Libraries of hardly available amino acids bearing a heteroaromatic ring (2-pyrimidyl, substituted 2-pyridyl or 2-thiazolyl) at the amino group were prepared using solid-phase synthesis on various resins. The synthesized compounds are structurally similar to some known antidiabetic drugs. The paper combines features of a review (elementary introduction to the solid-phase synthesis methodology and technique for beginners and selected methods from peptide chemistry) and step-by-step experimental protocols (tested by the authors) useful as a methodic tool. The presented protocols (immobilization and modification of amino acids, placing and removal of common protective groups) require no sophisticated equipment and may be useful as pictorial introductory tasks for students education. Pleiades Publishing, Ltd., 2010.
