Metal Ions as Cofactors for Aggregation of Therapeutic Peptide Salmon Calcitonin

The effects of multivalent metal ions (Cu²⁺/Zn²⁺/Al³⁺) on the aggregation of salmon calcitonin (sCT)a therapeutic peptide used worldwide in the treatment of osteoporosis and Paget’s diseasehave been studied <i>in vitro</i> using NMR (both solution state and solid state), TEM, ThT-fluorescence, and FT-IR spectroscopy. Overall, the various results indicated that the metal-ions-induced conformational transitions in the peptidemostly toward the β-sheetfacilitate the aggregation of sCT in solution. First, the solution NMR has been used to check the interaction between the peptide and the metal ions. Following this, the formation and characterization of calcitonin aggregates has been performed using TEM, solid state NMR, and FT-IR spectroscopy. The TEM and ThT-fluorescence results revealed that the sCT peptide incubated with Cu²⁺ and Zn²⁺ metal ions (in aqueous environment) forms globular aggregates, while that with Al³⁺ ions forms fibrils. The solid state NMR and FT-IR studies revealed the presence of a substantial amount of β-sheet content in sCT aggregates (formed in the presence of these metal ions) compared to the monomeric sCT, indicating that the metal binding is concomitant with conformational changes. The present study becomes crucial while prescribing this drug peptide under physio-pathological conditions associated with an abnormal accumulation of metal ions (Cu²⁺/Zn²⁺/Al³⁺) in the body (i.e., abnormal metal ion homeostasis)

Comprehensive metabolite profiling in distinct chemotypes of <i>Commiphora wightii</i>

<p><i>Commiphora wightii</i> (Arn.) Bhandari, known as guggul, produces a medicinally important gum resin which is used extensively by Ayurvedic physicians to treat various ailments. However, most of the studies on <i>C. wightii</i> have been limited to its gum resin. Comprehensive metabolic profiling of leaves, stem and gum resin samples was undertaken to analyse aqueous and non-aqueous metabolites from three distinct chemotypes (NBRI-101, NBRI-102 and NBRI-103) shortlisted from different agro-climatic zones. GC-MS, HPLC and NMR spectroscopy were used for comprehensive metabolomics. Multivariate analysis showed characteristic variation in quinic and citric acids, <i>myo</i>-inositol and glycine (aqueous metabolites) and 2,6-di-<i>tert</i>-butyl-phenol, <i>trans</i>-farnesol and guggulsterones (non-aqueous metabolites) amongst the three chemotypes. Quinic acid, citric acid and <i>myo</i>-ionositol were detected in substantial quantities from leaves and stem samples which provide opportunities for novel nutraceutical and pharmaceutical formulations. Quinic acid, from the leaves, was identified as a marker metabolite for early selection of high guggulsterones-yielding cultivars.</p