01365nas a2200169 4500008004100000022001400041245006600055210005600121260008100177300001600258490000700274520074200281100002301023700002401046700002801070856009701098 2008 eng d a1600-536800aDi-tert-butyl N,N `-(octahydropentalene-2,5-diyl) dicarbamate0 aDitertbutyl NN octahydropentalene25diyl dicarbamate a9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLANDbBLACKWELL PUBLISHINGcJUN aO1149-U28040 v643 a

In the molecule of the title compound, C18H32N2O4, the central bicyclo[3.3.0] octane (octahydropentalene) has a rigid ring junction. Both rings of the bicyclo[3.3.0] octane unit adopt an envelope conformation, and the flexible tert-butylcarbamoyl side chains each have an extended conformation. Such a constrained bicyclo[3.3.0] octane aliphatic template is of interest with respect to the design of novel self-assembling motifs. Molecules related by c-glide symmetry are linked via intermolecular N-H center dot center dot center dot O hydrogen bonds, forming a two-dimensional layer structure. Neighboring layers are weakly associated along the a axis due to the close approach of the tert-butylcarbamoyl groups (2.55 angstrom).

1 aKendhale, Amol, M.1 aGonnade, Rajesh, G.1 aSanjayan, Gangadhar, J. uhttps://library.ncl.res.in/content/di-tert-butyl-nn-octahydropentalene-25-diyl-dicarbamate-001522nas a2200181 4500008004100000022001400041245009800055210006900153260011000222300001600332490000700348520076700355100001401122700002601136700002701162700002801189856012301217 2011 eng d a1359-734500aDiversifying the structural architecture of synthetic oligomers: the hetero foldamer approach0 aDiversifying the structural architecture of synthetic oligomers  aTHOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLANDbROYAL SOC CHEMISTRYcAUG a11593-116110 v473 a

Conformationally ordered synthetic oligomers, also called ``foldamers'', have attracted considerable attention in recent years owing to their ability to mimic the structural architecture of biopolymers and also because of their potential applications in biomedical and material science fields. Until recently, the major focus in this area has been the development of oligomers featuring a single type of monomer building blocks. However, due to the enormous possibility of augmenting the conformational space available for oligomer design, the hetero foldamer approach has been introduced very recently. This feature article aims to describe foldamers with unique structural architectures, exclusively featuring heterogeneous backbones (hetero foldamers).

1 aRoy, Arup1 aPrabhakaran, Panchami1 aBaruah, Pranjal, Kumar1 aSanjayan, Gangadhar, J. uhttps://library.ncl.res.in/content/diversifying-structural-architecture-synthetic-oligomers-hetero-foldamer-approach-001813nas a2200265 4500008004100000022001400041245013800055210006900193260007500262300001400337520077500351653002601126653001901152653002001171653002601191100002401217700003301241700002201274700002201296700002301318700002401341700002401365700002801389856013001417 2016 eng d a1434-193X00aDisruption of native beta-turns: consequence of folding competition between native and orthanilic acid proline-based pseudo beta-turn0 aDisruption of native betaturns consequence of folding competitio aPOSTFACH 101161, 69451 WEINHEIM, GERMANYbWILEY-V C H VERLAG GMBHcMAR a1380-13883 a

Five tetrapeptides comprising beta-turn-forming elements and a pseudo beta-turn (C9 H-bonding) based on an SAntPro (orthanilic acid - proline) motif were designed and synthesized. Their extensive conformational investigation by single-crystal X-ray crystallography, solution-state 2D NMR spectroscopic, and nOe-restrained MD simulation studies revealed the formation of C14 or C9 folding and disruption of the native beta-turn (C10 H-bonding) architecture. The striking difference between the psi(psi(2)) angle of ``i + 2'' residues of native beta-turn and designed peptides suggest that formation of the native beta-turn is not favored. The results suggest that other turn-forming motifs can dramatically modulate the stability of the native beta-turn structure.

10aConformation analysis10ahydrogen bonds10aPeptidomimetics10astructure elucidation1 aIngole, Tukaram, S.1 aVijayadas, Kuruppanthara, N.1 aChaitanya, K., N.1 aKotmale, Amol, S.1 aGawade, Rupesh, L.1 aGonnade, Rajesh, G.1 aRajamohanan, P., R.1 aSanjayan, Gangadhar, J. uhttps://library.ncl.res.in/content/disruption-native-beta-turns-consequence-folding-competition-between-native-and-orthanilic02227nas a2200205 4500008004100000245013300041210006900174260000800243300001400251490000600265520145700271100002301728700002501751700002201776700002001798700002401818700001901842700002801861856013201889 2018 eng d00aDesign and synthesis of 2-amino-thiophene-tethered ureidopenicillin analogs with potentantibacterial and antitubercular activity0 aDesign and synthesis of 2aminothiophenetethered ureidopenicillin cMAR a3122-31260 v33 aUreidopenicillins are a class of penicillins which are antibiotics active against gram-negative bacteria. Herein, we report the synthesis of 2-aminothiophene-tethered ureidopenicillin analogues and their in vitro antibacterial and antitubercular activity. Intriguingly, unlike the reported ureidopenicillins which are active against gram-negative bacteria, the synthesised 2-aminothiophene-tethered ureidopenicillins were significantly active against Gram-positive bacterial strains and showed moderate inhibition towards gram-negative bacterial strains. Among all the analogs, compound 1b containing 2-aminothiophene moiety with minimum inhibitory concentration (MIC): 0.29, 0.32, > 10, > 10 mg/ml for Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa, respectively, showed better anti-bacterial profile as compared to cephalexin and equipotent to ampicillin and amoxicillin on gram-positive bacterial strains. All the derivatives were also screened for anti-TB activity against mycobacterium tuberculosis H37Ra. Among the series, cycloocta-thiophene-tethered cephalexin analog 3c displayed excellent antitubercular activity with MIC values 0.78 mg/ml. Low cytotoxicity and high selectivity index indicate the efficacy of 3c against mycobacterial infections. The results from present study offer a novel approach to modify the existing drug class of ureidopenicillins to yield antimicrobials with promising utility.1 aWagh, Mahendra, A.1 aBaravkar, Sachin, B.1 aJedhe, Ganesh, S.1 aBorkute, Rachna1 aChoudhari, Amit, S.1 aSarkar, Dhiman1 aSanjayan, Gangadhar, J. uhttps://library.ncl.res.in/content/design-and-synthesis-2-amino-thiophene-tethered-ureidopenicillin-analogs-potentantibacterial02635nas a2200277 4500008004100000022001400041245014100055210006900196260000900265300001400274490000600288520167100294653002101965653002001986653002002006653001502026653002202041100002502063700002302088700002302111700002402134700002002158700001902178700002802197856013202225 2019 eng d a2365-654900aDesign and synthesis of 2-amino-thiophene-proline-conjugates and their anti-tubercular activity against mycobacterium tuberculosis H37Ra0 aDesign and synthesis of 2aminothiopheneprolineconjugates and the cMAR  a2851-28570 v43 a

The emergence of extensively drug resistant tuberculosis (XDRTB) and multi-drug resistant tuberculosis (MDR-TB) has necessitated the development of new drugs with short chemotherapy treatment regime and cost effectiveness. To overcome these challenges, we are reporting the synthesis of a series of 2-amino-thiophene-proline-conjugates which show potent invino and ex-vivo anti-tubercular (anti-TB) activity against mycobacterium tuberculosis (rntb) H37Ra. The synthesis of these 2-amino-thiophene-proline-conjugates was carried out via solution phase peptide coupling reactions using methyl-2aminothiophene-3-carboxylate 8 as an intermediate obtained by modified gewald reaction. Intermediate 8 was coupled with different amino acids to obtain dipeptides 3, 4, 5, 6a and 7. Priliminary anti-TB assay data encoureaged us to synthesize modified proline derivatives 6b-6k via formation of a benzoxazinone intermediate 16. Most of these conjugates are active against mtb H37Ra in both active (A) and dormant (D) strains. They are also active against drug resistant mtb H37Ra strains. A trifluoroethyl ester analog, 6i was the most potent among the series [MIC 1 mu g/mL] along with 6f and 6g [MIC 2-6 mu g/mL]. Cytotoxicity studies suggested that, these compounds are less cytotoxic to human cell lines HeLa, MCF-7, HUVEC and hence possess high selectivity index (SI). Docking studies revealed that the binding mode of most active compounds 6i, 6g and 6f is in accordance with their bioactivity studies having docking score 8.969, 8.446 and 7.865, respectively. More- over, in sllico ADME properties suggest that all the compounds possess drug like properties.

10a2-aminothiophene10aAnti-tubercular10adocking studies10aInh A gene10aselectivity index1 aBaravkar, Sachin, B.1 aWagh, Mahendra, A.1 aNawale, Laxman, U.1 aChoudhari, Amit, S.1 aBhansali, Sujit1 aSarkar, Dhiman1 aSanjayan, Gangadhar, J. uhttps://library.ncl.res.in/content/design-and-synthesis-2-amino-thiophene-proline-conjugates-and-their-anti-tubercular-activity01636nas a2200277 4500008004100000022001400041245009300055210006900148260000900217300001600226490000600242520073400248653001300982653001200995653002101007653001301028653001301041100002601054700003001080700001801110700003501128700002001163700002401183700002801207856012301235 2019 eng d a2365-654900aDimedone-based rigid organic scaffold for organizing symmetrical helical peptide chains.0 aDimedonebased rigid organic scaffold for organizing symmetrical  cOCT  a11518-115220 v43 a

We describe herein design, synthesis and conformational investigations of polypeptides attached on a rigid dimedone template. Two identical peptide chains are attached on a single carbon containing dimedone as a scaffold. Dimedone assists in controlling the secondary interactions through strong intramolecular helical C-12 and C-15 membered bifurcated hydrogen bonding on both the peptide chains along with propagating the helical architecture of the peptide chains attached. There exists a C-6 hydrogen bonding for the single stranded peptides attached to dimedone. Extensive structural investigations involving single crystal X-ray diffraction, solution-state NMR and CD studies of oligopeptides have been undertaken.

10adimedone10aHelical10ahydrogen bonding10aPeptides10atemplate1 aMadica, Krishnaprasad1 aLakshmi, Jerripothula, K.1 aMadhu, Suresh1 aNadimpally, Krishna, Chaitanya1 aGonnade, Rajesh1 aJagadeesh, Bharatam1 aSanjayan, Gangadhar, J. uhttps://library.ncl.res.in/content/dimedone-based-rigid-organic-scaffold-organizing-symmetrical-helical-peptide-chains02186nas a2200265 4500008004100000022001400041245008200055210007000137260000800207490000700215520129400222653002501516653002801541653002601569653002301595653001501618100002201633700003501655700001901690700001801709700002201727700002501749700002801774856011801802 2023 eng d a1612-187200aDiscovery of SARS-CoV-2 inhibitors featuring novel histidine α-nitrile motif0 aDiscovery of SARSCoV2 inhibitors featuring novel histidine αnitr cDEC0 v203 a

As COVID-19 infection caused severe public health concerns recently, the development of novel antivirals has become the need of the hour. Main protease (Mpro) has been an attractive target for antiviral drugs since it plays a vital role in polyprotein processing and virus maturation. Herein we report the discovery of a novel class of inhibitors against the SARS-CoV-2, bearing histidine alpha-nitrile motif embedded on a simple dipeptide framework. In-vitro and in-silico studies revealed that the histidine alpha-nitrile motif envisioned to target the Mpro contributes to the inhibitory activity. Among a series of dipeptides synthesized featuring this novel structural motif, some dipeptides displayed strong viral reduction (EC50=0.48 mu M) with a high selectivity index, SI>454.54. These compounds also exhibit strong binding energies in the range of -28.7 to -34.2 Kcal/mol. The simple dipeptide structural framework, amenable to quick structural variations, coupled with ease of synthesis from readily available commercial starting materials are the major attractive features of this novel class of SARS-CoV-2 inhibitors. The histidine alpha-nitrile dipeptides raise the hope of discovering potent drug candidates based on this motif to fight the dreaded SARS-CoV-2.

10adipeptide inhibitors10ahistidine alpha-nitrile10aM-pro (main protease)10amolecular dynamics10aSARS-CoV-21 aGone, Nilu, Vijay1 aEnayathullah, Mohammed, Ghalib1 aThomas, Jessie1 aRathee, Parth1 aPrabhakar, Rajeev1 aBokara, Kiran, Kumar1 aSanjayan, Gangadhar, J. uhttps://library.ncl.res.in/content/discovery-sars-cov-2-inhibitors-featuring-novel-histidine-%CE%B1-nitrile-motif