Synthetic and antimicrobial studies on natural cyclopolypeptide from Caribbean marine-sponge and its analogs

Objective: A natural cyclic peptide, rolloamide, previously isolated from marine-sponge, was synthesized by coupling of tri and tetrapeptide units Boc­Phe-Pro- Val­OMe and Boc­Pro-Leu-Pro-Ile­OMe after proper deprotection at carboxyl and amino terminals followed by cyclization of linear heptapeptide segment. Design and Methodology: Solution phase technique was adopted for the synthesis of cycloheptapeptide. Required tri and tetrapeptide units were prepared by coupling of Boc-protected dipeptides viz. Boc­Phe-Pro­OH and Boc­Pro-Leu­OH with respective amino acid methyl ester hydrochloride Val-OMe.HCl and dipeptide methyl ester Pro-Ile-OMe. Cyclization of linear heptapeptide unit was done by p-nitrophenyl ester method. Similarly, two analogs of rolloamide were prepared by modification of tripeptide unit. The structures of synthesized cyclopeptide and its analogs were elucidated by spectral and elemental analysis. The newly synthesized peptide was subjected to antimicrobial screening and compared with biopotential of analogs. Results: Synthesis of cyclopeptide was accomplished with >84% yield utilizing diisopropylcarbodiimide (DIPC) as coupling agent. Newly synthesized peptide possessed promising activity against C. albicans and P. aeruginosa, K. pneumonia as compared to standard drugs, in addition to moderate activity against dermatophytes. Synthesized peptide analogs showed better antimicrobial potential against C. albicans and dermatophytes. Conclusions: Solution phase technique employing N,Ndiisopropylcarbodiimide (DIPC) and triethylamine (TEA) proved to be effective for the synthesis of natural cycloheptapeptide. N-methyl morpholine (NMM) was found to be a better base for cyclization of linear heptapeptide unit in comparison to TEA and pyridine. Promising antimicrobial potential was seen for newly synthesized cyclic peptide and its analogs.

Evaluation of vitamin D relationship with type 2 diabetes and systolic blood pressure

Objective: To investigate whether relationships existamong vitamin D, type 2 diabetes mellitus (T2DM), and blood pressure in Trinidadian subjects with T2DM. Research design and methods: This was a case­ controlled study to determine if vitamin D levels were lower in patients with T2DM. After data analysis, an exploratory hypothesis of vitamin D relationship to systolic blood pressure (SBP) was developed. Plasma calcifediol (25(OH)D) concentrations were used as a measurement for vitamin D levels and were determined by ELISA. Cholesterol levels were measured by an automated dry chemistry analyzer and blood pressure was measured using an automatic blood pressure monitor. Results: There was no significant difference ( p=0.139, n=76) in 25(OH)D levels between patients with T2DM and controls. Subjects with SBP above 130 mm Hg were 8 times more likely to have a 25(OH)D plasma concentration above 25 ng/mL (OR 7.9 (2.2 to 28.7)), and were 5 times (OR 4.7 (1.7 to 15.1)) more likely to have a 25(OH)D plasma concentration above 30 ng/mL (OR 7.5 (2.3­24.2)). Vitamin D levels moderately and positively correlated with SBP (rs=0.38, p=0.001). Conclusions: There was no significant difference in the 25(OH)D levels between patients with T2DM and controls ( p=0.139). Patients with SBP under 130 mm Hg were 8 times more likely to have a vitamin D level above 25 ng/mL (OR 7.9 (2.2 to 28.7)). Further investigations are required to examine the relationship between vitamin D and SBP.