Protein post-translational modification (PTM) occurs following their biosynthesis and is a key cellular event that defines their ultimate functional properties. It is an important control mechanism for display of biological functions of proteins often in a profound manner. It may switch on or off a protein’s function. Several studies have been conducted to understand their mechanisms, physiological pathways and functional properties. PTMs have been shown to alter structural, conformational and physicochemical properties of proteins. So far a variety of protein modifications have been detected in physiological systems. These involve covalent modifications of amino acids via their side chains, backbone peptide bonds and terminal moieties. Following PTM, proteins may become (a) pathologically toxic, (b) biologically active or inactive, (c) more or less susceptible to proteolytic processing, (d) increasingly/decreasingly bound to its partner protein/s, or (e) modified with altered protease activities. These changes may affect pathways linked to cell signaling/transduction, trafficking, storing, expression, binding and/or affinity. Any of these events may be linked to metabolic, growth and/or chronic dysfunctions with serious health consequences that may include cancer, cardiovascular disease, stroke, viral/bacterial/parasite infections, inflammation, thrombosis, diabetes; central nervous system related conditions. Some of the modifications are more prevalent physiologically and widely studied. However, in recent years additional PTMs have been described that are less common. These include glypiation, neddylayion, siderophorylation, sumoylation, AMPylation, Cholesteroylation and others which are also important. This manuscript provides a comprehensive review of these rare and unconventional types of protein modifications and their functional implications to health, metabolism and disease conditions.

Prader–Willi Syndrome (PWS) is a rare complex genetic disease that is associated with pathological disorders that include endocrine disruption, developmental, neurological, and physical problems as well as intellectual, and behavioral dysfunction. In early stage, PWS is characterized by respiratory distress, hypotonia, and poor sucking ability, causing feeding concern and poor weight gain. Additional features of the disease evolve over time. These include hyperphagia, obesity, developmental, cognitive delay, skin picking, high pain threshold, short stature, growth hormone deficiency, hypogonadism, strabismus, scoliosis, joint laxity, or hip dysplasia. The disease is associated with a shortened life expectancy. There is no cure for PWS, although interventions are available for symptoms management. PWS is caused by genetic defects in chromosome 15q11.2-q13, and categorized into three groups, namely Paternal deletion, Maternal uniparental disomy, and Imprinting defect. PWS is confirmed through genetic testing and DNA-methylation analysis. Studies revealed that at least two key proteins namely MAGEL-2 and NECDIN along with two proteases PCSK1 and PCSK2 are linked to PWS. Herein, we summarize our current understanding and knowledge about the role of these proteins and enzymes in various biological processes associated with PWS. The review also describes how loss and/or impairment of functional activity of these macromolecules can lead to hormonal disbalance by promoting degradation of secretory granules and via inhibition of proteolytic maturation of precursor-proteins. The present review will draw attention of researchers, scientists, and academicians engaged in PWS study and will help to identify potential targets and molecular pathways for PWS intervention and treatment.

Novel enediynyl tripeptides 2(a–c) in fully protected forms have been prepared via a sequence of palladium(0)-based Sonogashira coupling. The thermal reactivity of these peptides was shown to be dependent upon the nature of the side chain in the amino acids. Analysis of the CD-spectra of these peptides as well as the variation of chemical shifts with temperature revealed the presence of a β-sheet nucleating conformation in equilibrium with a conformation induced by H-bond formation between the CO and NH belonging to the enediynyl amino acid.

Enediynes continue to fascinate scientists working in various domains because of their structural complexity and fascinating biological mode of action. They represent a masterpiece of natures ingenuity. Besides the warhead which is the enediyne moiety, these molecules are equipped with a locking device, a delivery system and a chemical trigger for activation. Upon triggering, the molecules become active and undergo a thermal rearrangement that was disclosed in the early 70 by Masamune and Bergman and commonly known as Bergman cyclization. The reaction is believed to precede through a diradical benzenoid species (a p-benzyne). This review describes the various strategies employed for the synthesis of highly strained enediynes and dienediynes, both naturally occurring and the designed ones.