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1.
Biochemistry ; 60(36): 2704-2714, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34463474

RESUMO

In synthetic peptides containing Gly and coded α-amino acids, one of the most common practices to enhance their helical extent is to incorporate a large number of l-Ala residues along with noncoded, strongly foldameric α-aminoisobutyric acid (Aib) units. Earlier studies have established that Aib-based peptides, with propensity for both the 310- and α-helices, have a tendency to form ordered three-dimensional structure that is much stronger than that exhibited by their l-Ala rich counterparts. However, the achiral nature of Aib induces an inherent, equal preference for the right- and left-handed helical conformations as found in Aib homopeptide stretches. This property poses challenges in the analysis of a model peptide helical conformation based on chirospectroscopic techniques like electronic circular dichroism (ECD), a very important tool for assigning secondary structures. To overcome such ambiguity, we have synthesized and investigated a thermally stable 14-mer peptide in which each of the Aib residues of our previously designed and reported analogue ABGY (where B stands for Aib) is replaced by Cα-methyl-l-valine (L-AMV). Analysis of the results described here from complementary ECD and 1H nuclear magnetic resonance spectroscopic techniques in a variety of environments firmly establishes that the L-AMV-containing peptide exhibits a significantly stronger preference compared to that of its Aib parent in terms of conferring α-helical character. Furthermore, being a chiral α-amino acid, L-AMV shows an intrinsic, extremely strong bias for a quite specific (right-handed) screw sense. These findings emphasize the relevance of L-AMV as a more appropriate unit for the design of right-handed α-helical peptide models that may be utilized as conformationally constrained scaffolds.


Assuntos
Aminoácidos/química , Ácidos Aminoisobutíricos/química , Peptídeos/química , Valina/química , Dicroísmo Circular/métodos , Modelos Moleculares , Conformação Proteica em alfa-Hélice , Estrutura Secundária de Proteína
2.
J Biomol Struct Dyn ; : 1-14, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38373072

RESUMO

Breast cancer is considered to be happened due to genetic aberration. Out of several genes expressed, it is found that cadherin 1, type 1 (CDH1) is responsible in several ways to control the metabolic order in human. Deregulation of the function of protein E-cadherin, expressed from CDH1 plays an important role in lobular breast cancer. In order to understand the root cause of this recent claim, we focus on CDH1 gene: whether the genetic information translated due to any deviation/alteration/modification in its sequence is related to the occurrence of the different types breast cancer. Towards this end, quantitative analysis of different biophysical and bio-chemical properties of CDH1 gene in genomic and proteomic levels from the available genomic (cDNA) sequences of CDH1 gene (obtained from the COSMIC Database for 78 patients, suffering from various types of breast cancer) clearly emphasizes that alternation/modification in the sequence of the CDH1 gene can be detrimental. Furthermore, Random forest, K-nearest neighbour and stochastic gradient descent (SGD) algorithms are applied on the derived dataset to classify the types of breast cancer, and to validate our hypothesis regarding the acute role of CDH1 as potential bio marker for breast cancer. Analysis of the mutated CDH1 gene sequences, and their related parameters using aforesaid machine learning techniques clearly establish that CDH1 gene can take the deterministic role in predicting the chances of occurrences of different types of breast cancer with an accuracy of >90%. Such an observation opens a new paradigm in diagnostic approach of breast cancer.Communicated by Ramaswamy H. Sarma.

3.
Nat Prod Bioprospect ; 14(1): 15, 2024 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-38310179

RESUMO

A type of high molecular weight bioactive polymers called exopolysaccharides (EPS) are produced by thermophiles, the extremophilic microbes that thrive in acidic environmental conditions of hot springs with excessively warm temperatures. Over time, EPS became important as natural biotechnological additives because of their noncytotoxic, emulsifying, antioxidant, or immunostimulant activities. In this article, we unravelled a new EPS produced by Staphylococcus sp. BSP3 from an acidic (pH 6.03) San Pedro hot spring (38.1 °C) located in the central Andean mountains in Chile. Several physicochemical techniques were performed to characterize the EPS structure including Scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDS), Atomic Force Microscopy (AFM), High-Performance Liquid Chromatography (HPLC), Gel permeation chromatography (GPC), Fourier Transform Infrared Spectroscopy (FTIR), 1D Nuclear Magnetic Resonance (NMR), and Thermogravimetric analysis (TGA). It was confirmed that the amorphous surface of the BSP3 EPS, composed of rough pillar-like nanostructures, is evenly distributed. The main EPS monosaccharide constituents were mannose (72%), glucose (24%) and galactose (4%). Also, it is a medium molecular weight (43.7 kDa) heteropolysaccharide. NMR spectroscopy demonstrated the presence of a [→ 6)-⍺-D-Manp-(1 → 6)-⍺-D-Manp-(1 →] backbone 2-O substituted with 1-⍺-D-Manp. A high thermal stability of EPS (287 °C) was confirmed by TGA analysis. Emulsification, antioxidant, flocculation, water-holding (WHC), and oil-holding (OHC) capacities are also studied for biotechnological industry applications. The results demonstrated that BSP3 EPS could be used as a biodegradable material for different purposes, like flocculation and natural additives in product formulation.

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