26061-06-3Relevant academic research and scientific papers
Synthesis and Structure-Activity Relationships of Ring-Opened Bengamide Analogues against Methicillin-Resistant Staphylococcus aureus?
Yu, Chen-Xi,Wei, Bing-Yan,Kong, Xue-Qing,Yang, Cai-Guang,Nan, Fa-Jun
supporting information, p. 671 - 676 (2021/02/12)
Methicillin-resistant Staphylococcus aureus (MRSA) has become a major threat on public health because of the increase of clinically isolated strains that exhibit resistance to many antibiotics. Therefore, development of new antibiotics for the treatment of MRSA infection is a sustained challenge. We have previously identified a ring-opened bengamide analogue L472-2 that displays moderate activity against the growth of S. aureus. In our previous work, we started from L472-2 and identified a class of analogues containing alkynyl groups which have the potential to activate SaClpP activity but moderate antibacterial activity. Herein, we focused on the antibacterial activity of L472-2, and a novel series of ring-opened bengamide analogues were synthesized and their activities were evaluated against MRSA. By conducting a compact analysis of the structure-activity relationships (SAR) of these analogues, we found that an adamantane ethanol ester bengamide 2j showed excellent antibacterial activity towards six S. aureus strains, including MRSA, while it does not activate ClpP. Therefore, these bengamide analogues represent a new class of candidates that suppress MRSA viability.
Tripeptide-induced modulation of mesenchymal stem cell biomechanics stimulates proliferation and wound healing
Ali, Rafat,Chattopadhyay, Naibedya,Kulkarni, Chirag,Kulkarni, Manish M.,Porwal, Konica,Sharma, Swati,Tewari, Deepshikha,Verma, Sandeep
supporting information, p. 3043 - 3046 (2020/03/18)
We demonstrate the ability of two tripeptides to promote proliferation and modulate the mechanical properties of human mesenchymal stem cells (hMSCs). Notably, Young's modulus of peptide-treated hMSCs was found to be ～2 fold higher compared to the control group. These peptides promoted wound healing in hMSCs, without stimulating osteogenic and adipogenic differentiation, thus showing high potential in vascular tissue engineering applications.
Chemical synthesis of tripeptide thioesters for the biotechnological incorporation into the myxobacterial secondary metabolite argyrin via mutasynthesis
Siebert, David C.B.,Sommer, Roman,Pogorevc, Domen,Hoffmann, Michael,Wenzel, Silke C.,Müller, Rolf,Titz, Alexander
supporting information, p. 2922 - 2929 (2019/12/23)
The argyrins are secondary metabolites from myxobacteria with antibiotic activity against Pseudomonas aeruginosa. Studying their structure–activity relationship is hampered by the complexity of the chemical total synthesis. Mutasynthesis is a promising approach where simpler and fully synthetic intermediates of the natural product’s biosynthesis can be biotechnologically incorporated. Here, we report the synthesis of a series of tripeptide thioesters as mutasynthons containing the native sequence with a dehydroalanine (Dha) Michael acceptor attached to a sarcosine (Sar) and derivatives. Chemical synthesis of the native sequence D-Ala-Dha-Sar thioester required revision of the sequential peptide synthesis into a convergent strategy where the thioester with sarcosine was formed before coupling to the Dha-containing dipeptide.
Engineered Substrate for Cyclooxygenase-2: A Pentapeptide Isoconformational to Arachidonic Acid for Managing Inflammation
Kaur, Baljit,Kaur, Manpreet,Kaur, Navjot,Garg, Saweta,Bhatti, Rajbir,Singh, Palwinder
, p. 6363 - 6376 (2019/07/08)
Beyond the conventional mode of working of anti-inflammatory agents through enzyme inhibition, herein, COX-2 was provided with an alternate substrate. A proline-centered pentapeptide isoconformational to arachidonic acid, which exhibited appreciable selectivity for COX-2, overcoming acetic acid- and formalin-induced pain in rats to almost 80%, was treated as a substrate by the enzyme. Remarkably, COX-2 metabolized the pentapeptide into small fragments consisting mainly of di- and tripeptides that ensured the safe breakdown of the peptide under in vivo conditions. The kinetic parameter Kcat/Km for COX-2-mediated metabolism of the peptide (6.3 × 105 M-1 s-1) was quite similar to 9.5 × 105 M-1 s-1 for arachidonic acid. Evidenced by the molecular dynamic studies and the use of Y385F COX-2, it was observed that the breakage of the pentapeptide has probably been taken place through H-bond activation of the peptide bond by the side chains of Y385 and S530.
Copper(I)-Mediated Denitrogenative Macrocyclization for the Synthesis of Cyclic α3β-Tetrapeptide Analogues
Chen, Chun-Chi,Wang, Sheng-Fu,Su, Yung-Yu,Lin, Yuya A.,Lin, Po-Chiao
, p. 1326 - 1337 (2017/06/23)
A copper(I)-mediated denitrogenative reaction has been successfully developed for the preparation of cyclic tetrapeptides. The key reactive intermediate, ketenimine, triggers intramolecular cyclization through attack of the terminal amine group to generate an internal β-amino acid with an amidine linkage. The chemistry developed herein provides a new synthetic route for the preparation of cyclic α3β-tetrapeptide analogues that contain important biological properties and results in rich structural information being obtained for conformational studies. With the success of this copper(I)-catalyzed macrocyclization, two histone deacetylase inhibitor analogues consisting of the cyclic α3β-tetrapeptide framework have been successfully synthesized.
Synthesis and anti-cancer activity of naturally occurring 2,5-diketopiperazines
Mollica, Adriano,Costante, Roberto,Fiorito, Serena,Genovese, Salvatore,Stefanucci, Azzurra,Mathieu, Veronique,Kiss, Robert,Epifano, Francesco
, p. 91 - 97 (2014/08/18)
Three naturally occurring oxyprenylated diketopiperazines were synthesized and preliminarily tested as growth inhibitory agents in vitro against various cancer cell lines. The compounds were tested on six human cancer cell lines with different sensitivity to proapoptotic stimuli using the MTT colorimetric assay. The data revealed that of the chemicals under study only deoxymicelianamide (11) displayed the highest activity, recording mean IC50 growth inhibitory values ranging from 2 to 23 μM. A comparative study with the non-geranylated saturated derivative of (11) revealed the importance of the presence of the geranyloxy side chain and the exocyclic 2,5-DPK double bond moiety for the observed activity.
Design, synthesis and preliminary evaluation of α-sulfonyl γ-(glycinyl-amino)proline peptidomimetics as matrix metalloproteinase inhibitors
Zhang, Jian,Li, Xiaoyang,Jiang, Yuqi,Feng, Jinhong,Li, Xiaoguang,Zhang, Yingjie,Xu, Wenfang
, p. 3055 - 3064 (2014/05/20)
A series of novel α-sulfonyl γ-(glycinyl-amino)proline peptidomimetic derivatives were designed, synthesized and assayed for their activities against matrix metalloproteinase-2 (MMP-2), aminopeptidase N (APN)/CD13 and HDACs. The results indicated that all the compounds exhibited highly selective inhibition against MMP-2 as compared with APN and HDACs. The antiproliferative activities of some compounds against SKOV3, HL60 and A549 cells were also investigated. Comparing with the control LY52, compound 12u, with excellent activity both in the enzymatic inhibition assay and cell-based assay, could be used as lead compound for the further development of MMP inhibitors.
Aerobic amide bond formation with N-hydroxysuccinimide
Yao, Haoyi,Yamamoto, Kana
supporting information; experimental part, p. 1542 - 1545 (2012/09/08)
Breathe easy: Molecular oxygen is one of the most abundant, atom-efficient, and economical oxidants. An aerobic oxidative amide formation from aldehydes and amines is reported. The method uses a catalytic amount of Co(OAc) 2 and N-hydroxysuccinimide as reaction promoters. It is applicable to chiral substrates without loss of their optical purity. Copyright
Direct C-H alkylation of naphthoquinones with amino acids through a revisited Kochi-Anderson radical decarboxylation: Trends in reactivity and applications
Naturale, Guillaume,Lamblin, Marc,Commandeur, Claude,Dessolin, Jean,Felpin, Francois-Xavier
supporting information, p. 5774 - 5788,15 (2020/09/15)
In our ongoing research program into the discovery of new anticancer drugs, we were interested in the preparation of naphthoquinone scaffolds bearing aminoalkyl side-chains. Following this aim, we revisited the Kochi-Anderson radical decarboxylation of amino acids in order to set up a versatile route to the direct functionalization of naphthoquinones. The best reaction conditions were applied to a selected series of compounds in a systematic methodological study which allowed us to establish important trends in reactivity. We found that α-substituted β-amino acids were the most suitable substrates for the radical addition. In contrast, α-amino acids gave modest results. The influence of the amine protecting groups on the reaction outcome has also been studied. This practical procedure allows the introduction of various unsymmetrical moieties, including orthogonally protected linear aminoalkyl chains or chiral dipeptidic chains, and opens the door to a wide scope of easily accessible chemical diversity.
Polyketide synthase thioesterases catalyze rapid hydrolysis of peptidyl thioesters
Wang, Meng,Opare, Peter,Boddy, Christopher N.
supporting information; experimental part, p. 1413 - 1415 (2009/10/15)
Polyketide synthase (PKS) thioesterases (TEs) catalyze the macrocyclization of linear acyl chains into macrolactones. Herein we show that peptide based substrates are processed by PKS TEs with greater catalytic efficiency than more native like acyl substrates. This result strengths the link between PKS and non-ribosomal peptide synthetase systems and provides a new tool for studying PKS TEs.
