02632nas a2200265   4500008004100000022001400041245022300055210006900278260010300347300001400450490000700464520147500471100002301946700002901969700003901998700002902037700001702066700002502083700002702108700002002135700002302155700003202178700002502210856013102235       2015                        eng d  a1535-947600aDevelopment of diagnostic fragment ion library for glycated peptides of human serum albumin: targeted quantification in prediabetic, diabetic, and microalbuminuria plasma by parallel reaction monitoring, SWATH, and MSE0 aDevelopment of diagnostic fragment ion library for glycated pept  a9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USAbAMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INCcAUG  a2150-21590 v143 a<p>Human serum albumin is one of the most abundant plasma proteins that readily undergoes glycation, thus glycated albumin has been suggested as an additional marker for monitoring glycemic status. Hitherto, only Amadori-modified peptides of albumin were quantified. In this study, we report the construction of fragment ion library for Amadori-modified lysine (AML), N(epsilon)-(carboxymethyl) lysine (CML)-, and N(epsilon)-(carboxyethyl) lysine (CEL)-modified peptides of the corresponding synthetically modified albumin using high resolution accurate mass spectrometry (HR/AM). The glycated peptides were manually inspected and validated for their modification. Further, the fragment ion library was used for quantification of glycated peptides of albumin in the context of diabetes. Targeted Sequential Window Acquisition of all THeoretical Mass Spectra (SWATH) analysis in pooled plasma samples of control, prediabetes, diabetes, and microalbuminuria, has led to identification and quantification of 13 glycated peptides comprised of four AML, seven CML, and two CEL modifications, representing nine lysine sites of albumin. Five lysine sites namely K549, K438, K490, K88, and K375, were observed to be highly sensitive for glycation modification as their respective m/z showed maximum fold change and had both AML and CML modifications. Thus, peptides involving these lysine sites could be potential novel markers to assess the degree of glycation in diabetes.</p>1 aKorwar, Arvind, M.1 aVannuruswamy, Garikapati1 aJagadeeshaprasad, Mashanipalya, G.1 aJayaramaiah, Ramesha, H.1 aBhat, Shweta1 aRegin, Bhaskaran, S.1 aRamaswamy, Sureshkumar1 aGiri, Ashok, P.1 aMohan, Viswanathan1 aBalasubramanyam, Muthuswamy1 aKulkarni, Mahesh, J.  uhttp://library.ncl.res.in/content/development-diagnostic-fragment-ion-library-glycated-peptides-human-serum-albumin-targeted-002276nas a2200337   4500008004100000022001400041245011600055210006900171260000800240300001400248490000700262520120700269653000601476653000601482653002101488653001101509653003001520653002801550653003101578100001801609700001701627700002501644700002401669700001701693700002301710700002401733700002201757700002201779700001901801856011801820       2022                        eng d  a1381-199100aDetection of a target protein (GroEl2) in Mycobacterium tuberculosis using a derivative of 1,2,4-triazolethiols0 aDetection of a target protein GroEl2 in Mycobacterium tuberculos  cOCT  a2535-25480 v263 a<p>
	Herein, we identified a potent lead compound RRA2, within a series of 54 derivatives of 1,2,4-triazolethiols (exhibit good potency as an anti-mycobacterial agents) against intracellular Mycobacterium tuberculosis (Mtb). Compound RRA2 showed significant mycobactericidal activity against active stage Mycobacterium bovis BCG and Mtb with minimum inhibitory concentration (MIC) values of 2.3 and 2.0 mu g/mL, respectively. At MIC value, RRA2 compound yielded 0.82 log reduction of colony-forming unit (cfu) against non-replicating Mtb. Furthermore, RRA2 compound was selected for further target identification due to the presence of alkyne group, showing higher selectivity index (&gt; 66.66 +/- 0.22, in non-replicating stage). Using ``click'' chemistry, we synthesized the biotin linker-RRA2 conjugate, purified with HPLC method and confirmed the conjugation of biotin linker-RRA2 complex by HR-MS analysis. Furthermore, we successfully pulled down and identified a specific target protein GroEl2, from Mtb whole-cell extract. Furthermore, computational molecular modeling indicated RRA2 could interact with GroEl2, which explains the structure-activity relationship observed in this study.</p>
10a110a210a4-triazolethiols10aGroEl210aMycobactericidal activity10aMycobacterium bovis BCG10aMycobacterium tuberculosis1 aSarkar, Sampa1 aSwami, Sagar1 aSoni, Sarvesh, Kumar1 aHolien, Jessica, K.1 aKhan, Arshad1 aKorwar, Arvind, M.1 aLikhite, Anjali, P.1 aJoshi, Ramesh, A.1 aJoshi, Rohini, R.1 aSarkar, Dhiman  uhttp://library.ncl.res.in/content/detection-target-protein-groel2-mycobacterium-tuberculosis-using-derivative-124