108283-49-4Relevant academic research and scientific papers
Fmoc-chemistry of a stable phosphohistidine analogue
McAllister, Tom E.,Nix, Michael G.,Webb, Michael E.
, p. 1297 - 1299 (2011)
We report the synthesis of the phosphohistidine analogue, Fmoc-4-diethylphosphonotriazolylalanine 5 and its incorporation into peptides. Our synthesis of 5 has enabled us to demonstrate that the analogue is compatible with Fmoc-solid phase peptide synthesis (SPPS) conditions. Standard cleavage conditions yield the diethyl phosphonate-protected peptide, however this can be subsequently deprotected using trimethylsilyl bromide to yield the free phosphonic acid-containing peptides.
Efficient synthesis of conformationally constrained, amino- triazoloazepinone-containing di- and tripeptides via a one-pot Ugi-Huisgen tandem reaction
Barlow,Jida,Tourwe,Ballet
, p. 6986 - 6989 (2014)
Herein we describe a catalyst-free procedure employing an Ugi-4CR between a β-azido-α-amino acid, propargylamine, an isocyanide and an aldehyde, followed by a thermal azide-alkyne Huisgen cycloaddition to generate a 16-member library of amino-triazoloazepinone-bearing di- and tripeptides with up to four points of diversification and high atom economy. This journal is the Partner Organisations 2014.
Uracil-amino acid as a scaffold for β-sheet peptidomimetics: Study of photophysics and interaction with BSA protein
Bag, Subhendu Sekhar,Yashmeen, Afsana
, p. 5387 - 5392 (2017)
We report herein the uracil-di-aza-amino acid (UrAA) as a new family of molecular scaffold to induce β-hairpin structure with H-bonded β-sheet conformation in a short peptide. This has been demonstrated in two conceptual fluorescent pentapeptides wherein triazolylpyrenyl alanine and/or triazolylmethoxynapthyl alanine (TPyAlaDo and/or TMNapAlaDo) are embedded into two arms of the uracil-amino acid via an intervening leucine. Conformational analysis by CD, IR, variable temperature and 2D NMR spectroscopy reveals the β-hairpin structures for both the peptides. Study of photophysical property reveals that the pentapeptide containing fluorescent triazolyl unnatural amino acids TMNapAlaDo and TPyAlaDo at the two termini exhibits dual path entry to exciplex emission-either via FRET from TMNapAlaDo to TPyAlaDo or via direct excitation of a FRET acceptor, TPyAlaDo. The other pentapeptide with TPyAlaDo/TPyAlaDo pair shows excimer emission. Furthermore, both the peptides maintaining their fundamental photophysics are found to interact with BSA as only a test biomolecule.
Simple preparation of new [18F]F-labeled synthetic amino acid derivatives with two click reactions in one-pot and SPE purification
Yook, Cheol-Min,Lee, Sang Ju,Oh, Seung Jun,Ha, Hyun-Joon,Lee, Jong Jin
, p. 317 - 326 (2015)
New [18F]fluorinated 1,2,3-triazolyl amino acid derivatives were efficiently prepared from Huisgen 1,3-dipolar cycloaddition reactions, well known as click reaction. We developed two simultaneous click reactions in one-pot with a simple solid-p
Triazolo-β-aza-ε-amino acid and its aromatic analogue as novel scaffolds for β-turn peptidomimetics
Bag, Subhendu Sekhar,Jana, Subhashis,Yashmeen, Afsana,De, Suranjan
, p. 5242 - 5245 (2015)
Triazolo-β-aza-ε-amino acid and its aromatic analogue (AlTAA/ArTAA) in the peptide backbone mark a novel class of conformationally constrained molecular scaffolds to induce β-turn conformations. This was demonstrated forAlTAA in a Leu-enkephalin analogue and in a designed pentapeptide wherein the FRET process was established. Restricted rotation induced chirality and turn conformation into the achiral aromatic amino acid scaffold,ArTAA, which in a short tripeptide backbone acted as a β-turn mimic as a β-sheet folding nucleator. This journal is
Structure-based development of an osteoprotegerin-like glycopeptide that blocks RANKL/RANK interactions and reduces ovariectomy-induced bone loss in mice
Liu, Chao,Chen, Xiao,Zhi, Xin,Weng, Weizong,Li, Quan,Li, Xiang,Zou, Yan,Su, Jiacan,Hu, Hong-Gang
, p. 661 - 672 (2018)
Osteoporosis is a metabolic bone disease characterized by low bone mass and micro-architectural deterioration of bone, for which the underlying mechanism is an imbalance between bone resorption and bone remodeling. The protein-protein interactions between receptor activator of nuclear factor-κB ligand (RANKL), RANK (its receptor), and osteoprotegerin (OPG), are known to mediate the development and activation of osteoclasts in bone remodeling, and are regarded as a pivotal therapeutic target for the treatment of osteoporosis. Herein, we disclose the successful development of a novel glycopeptide (OM-2), the structure of which is based on the key interacting sites of the reported RANKL and OPG crystal structure. OM-2 exhibited potent binding affinity with RANKL and resistance to degradation by protease enzymes. It also blocked RANKL/RANK interactions, and inhibited osteoclastogenesis in vitro. In vivo studies confirmed that OM-2 could effectively reduce bone loss and inhibit osteoclast activation in ovariectomized (OVX) mice at a dosage of 20.0 mg/kg/day. Accordingly, OM-2 is suggested as a therapeutic candidate for postmenopausal osteoporosis (PMOP) and osteoclastogenesis-related diseases like rheumatoid arthritis (RA). More importantly, its identification validates our structure-based strategy for the development of drugs that target the RANKL/RANK/OPG system.
Enantioselective Anion Recognition by Chiral Halogen-Bonding [2]Rotaxanes
Lim, Jason Y. C.,Marques, Igor,Félix, Vítor,Beer, Paul D.
, p. 12228 - 12239 (2017)
The application of chiral interlocked host molecules for discrimination of guest enantiomers has been largely overlooked, which is surprising given their unique three-dimensional binding cavities capable of guest encapsulation. Herein, we combined the stringent linear geometric interaction constraints of halogen bonding (XB), the noncovalent interaction between an electrophilic halogen atom and a Lewis base, with highly preorganized and conformationally restricted chiral cavities of [2]rotaxanes to achieve enantioselective anion recognition. Representing the first detailed investigation of the use of chiral XB rotaxanes for this purpose, extensive 1H NMR binding studies and molecular dynamics (MD) simulation experiments revealed that the chiral rotaxane cavity significantly enhances enantiodiscrimination compared to the non-interlocked free axle and macrocycle components. Furthermore, by examining the enantioselectivities of a family of structurally similar XB [2]rotaxanes containing different combinations of chiral and achiral macrocycle and axle components, the dominant influence of the chiral macrocycle in our rotaxane design for determining the effectiveness of chiral discrimination is demonstrated. MD simulations reveal the crucial geometric roles played by the XB interactions in orientating the bound enantiomeric anion guests for chiral selectivity, as well as the critical importance of the anions' hydration shells in governing binding affinity and enantiodiscrimination.
A short synthetic approach to chiral serine azido derivatives
Panda, Gautam,Rao, N. Venugopal
, p. 714 - 716 (2004)
We report a new synthetic methodology for the synthesis of chiral serine azido derivatives through a conversion of N-protected (Boc, Cbz and Fmoc) serine amino acid into its corresponding Weinreb amide. Thus, acidity of the α-proton of the serine is reduced and it allows nucleophilic addition reaction onto Weinreb amide to furnish chiral serine azido derivatives.
Clickable Cγ-azido(methylene/butylene) peptide nucleic acids and their clicked fluorescent derivatives: Synthesis, DNA hybridization properties, and cell penetration studies
Jain, Deepak R.,Ganesh, Krishna N.
, p. 6708 - 6714 (2014)
Synthesis, characterization, and DNA complementation studies of clickable Cγ-substituted methylene (azm)/butylene (azb) azido PNAs show that these analogues enhance the stability of the derived PNA:DNA duplexes. The fluorescent PNA oligomers synthesized by their click reaction with propyne carboxyfluorescein are seen to accumulate around the nuclear membrane in 3T3 cells.
pDobz/pDobb protected diaminodiacid as a novel building block for peptide disulfide-bond mimic synthesis
Liu, Chao,Zou, Yan,Hu, Honggang,Jiang, Yunyun,Qin, Luping
, p. 5438 - 5444 (2019)
The diaminodiacid strategy has been widely studied in the chemical synthesis of peptide disulfide bond mimics. Diaminodiacid building blocks, which are key intermediates, are currently under the spotlight. However, one technical bottleneck inherent in existing building blocks is the contamination problem caused by the heavy metal reagents during the deprotection process, which makes the peptides less suitable for pharmaceutical use. Herein, we describe the successful development of a p-dihydroxyborylbenzyloxycarbonyl pinacol ester (pDobz)- and p-dihydroxyborylbenzyl pinacol ester (pDobb)-based novel diaminodiacid building block that can be easily deprotected via mild treatment with amine oxide. Its efficiency and practicability were also confirmed by the total synthesis of contryphan-Vn disulfide bond mimic. The results suggested that this novel diaminodiacid building block has satisfactory Fmoc SPPS compatibility, yet only required a facile, rapid, and metal-free deprotection process. We believe this novel diaminodiacid building block could promote further development of the diaminodiacid strategy.
