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Compartmentalization protected biomolecules from the fluctuating environments of early Earth. Although contemporary cells mostly use phospholipid‐based bilayer membranes, the utility of non‐bilayer compartments was not ruled out during the prebiotic and modern eras. In the present study, we demonstrated the prebiotic synthesis of lipidated cationic amino acid‐based amphiphiles [lauryl ester of lysine (LysL); ornithine (OrnL); and 2,4‐diamino butyric acid (DabL)] using model dry‐down reaction. These amphiphiles self‐assemble into micellar membranes. However, the OrnL and DabL‐based micelles undergo pH‐responsive transformation to lipid droplet‐like morphologies, a modelcompartment in the prebiotic Earth. These cationic droplets encapsulated prebiotic molecules (isoprene) and assisted electron transfer reaction to synthesize isoprenoid derivatives at primitive Earth conditions. The self‐assembly of prebiotic amphiphiles, their transformation to droplet compartments, and droplet‐assisted C−C bond formation reaction might have helped the evolution to synthesize various biomolecules required for the origin of life. [ABSTRACT FROM AUTHOR]

Amyloid fibril formation of proteins is of great concern in neurodegenerative disease and can be detrimental to the storage and stability of biologics. Recent evidence suggests that insulin fibril formation reduces the efficacy of type II diabetes management and may lead to several complications. To develop anti‐amyloidogenic compounds of endogenous origin, we have utilized the hydrogen bond anchoring, π stacking ability of porphyrin, and investigated its role on the inhibition of insulin amyloid formation. We report that hydroxylation and metal removal from the heme moiety yields an excellent inhibitor of insulin fibril formation. Thioflavin T, tyrosine fluorescence, Circular Dichorism (CD) spectroscopy, Field emission scanning electron microscopy (FESEM) and molecular dynamics (MD) simulation studies suggest that hematoporphyrin (HP) having hydrogen bonding ability on both sides is a superior inhibitor compared to hemin and protoporphyrin (PP). Experiments with hen egg white lysozyme (HEWL) amyloid fibril formation also validated the efficacy of endogenous porphyrin based small molecules. Our results will help to decipher a general therapeutic strategy to counter amyloidogenesis. [ABSTRACT FROM AUTHOR]

Amyloid fibril formation of proteins is of great concern in neurodegenerative disease and can be detrimental to the storage and stability of biologics. Recent evidence suggests that insulin fibril formation reduces the efficacy of type II diabetes management and may lead to several complications. To develop anti-amyloidogenic compounds of endogenous origin, we have utilized the hydrogen bond anchoring, π stacking ability of porphyrin, and investigated its role on the inhibition of insulin amyloid formation. We report that hydroxylation and metal removal from the heme moiety yields an excellent inhibitor of insulin fibril formation. Thioflavin T, tyrosine fluorescence, Circular Dichorism (CD) spectroscopy, Field emission scanning electron microscopy (FESEM) and molecular dynamics (MD) simulation studies suggest that hematoporphyrin (HP) having hydrogen bonding ability on both sides is a superior inhibitor compared to hemin and protoporphyrin (PP). Experiments with hen egg white lysozyme (HEWL) amyloid fibril formation also validated the efficacy of endogenous porphyrin based small molecules. Our results will help to decipher a general therapeutic strategy to counter amyloidogenesis., (© 2021 Wiley-VCH GmbH.)