Single Amino Acid Based Self-Assemblies of Cysteine and Methionine

We report for the very first time self-assembly of Cysteine and Methionine to discrenible strucutres under neutral condition. To get insights into the structure formation, thioflavin T and Congo red binding assays were done which revealed that aggregates may not have amyloid like characteristics. The nature of interactions which lead to such self-assemblies was purported by coincubating assemblies in urea and mercaptoethanol. Further interaction of aggregates with short amyloidogenic dipeptide diphenylalanine (FF) was assessed. While cysteine aggregates completely disrupted FF fibres, methionine albeit triggered fibrillation. The cytotoxicity assays of cysteine and methionine structures were performed on Human Neuroblastoma IMR-32 cells which suggested that aggregates are not cytotoxic in nature and thus, may not have amyloid like etiology. The results presented in the manuscript are striking, since to the best of our knowledge,this is the first report which demonstrates that even non-aromatic amino acids (cysteine and methionine) can undergo spontaneous self-assembly to form ordered aggregates.

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Single Amino Acid Based Self-Assemblies of Cysteine and Methionine

10.26434/chemrxiv.5972173 ◽

2018 ◽

Author(s):

Nidhi Gour ◽

Bharti Koshti ◽

Chandra Kanth P. ◽

Dhruvi Shah ◽

Vivek Shinh Kshatriya ◽

...

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Self Assembly ◽

Aromatic Amino Acids ◽

Neutral Condition ◽

Single Amino Acid ◽

First Report ◽

First Time

We report for the very first time self-assembly of Cysteine and Methionine to discrenible strucutres under neutral condition. The nature of interactions which lead to such self-assemblies was purported by coincubating assemblies in urea and mercaptoethanol. Further interaction of aggregates with short amyloidogenic dipeptide diphenylalanine (FF) was assessed. While cysteine aggregates completely disrupted FF fibres, methionine albeit triggered fibrillation. . The results presented in the manuscript are striking, since to the best of our knowledge,this is the first report which demonstrates that even non-aromatic amino acids (cysteine and methionine) can undergo spontaneous self-assembly to form ordered aggregates.

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Single Amino Acid Based Self-Assemblies of Cysteine and Methionine

10.26434/chemrxiv.5972173.v3 ◽

2018 ◽

Author(s):

Nidhi Gour ◽

Bharti Koshti ◽

Chandra Kanth P. ◽

Dhruvi Shah ◽

Vivek Shinh Kshatriya ◽

...

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Self Assembly ◽

Aromatic Amino Acids ◽

Neutral Condition ◽

Single Amino Acid ◽

First Report ◽

First Time

We report for the very first time self-assembly of Cysteine and Methionine to discrenible strucutres under neutral condition. The nature of interactions which lead to such self-assemblies was purported by coincubating assemblies in urea and mercaptoethanol. Further interaction of aggregates with short amyloidogenic dipeptide diphenylalanine (FF) was assessed. While cysteine aggregates completely disrupted FF fibres, methionine albeit triggered fibrillation. . The results presented in the manuscript are striking, since to the best of our knowledge,this is the first report which demonstrates that even non-aromatic amino acids (cysteine and methionine) can undergo spontaneous self-assembly to form ordered aggregates.

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Unusual Aggregation Properties of Single Amino Acid L-Lysine Hydrochloride

10.26434/chemrxiv.14152976 ◽

2021 ◽

Author(s):

Bharti Koshti ◽

Ramesh Singh ◽

Vivekshinh Kshtriya ◽

Shanka Walia ◽

Dhiraj Bhatia ◽

...

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Self Assembly ◽

Short Term Memory ◽

Deionized Water ◽

The Body ◽

The Self ◽

Single Amino Acid ◽

Maple Syrup ◽

Self Assembling

. The self-assembly of single amino acids is very important topic of research since there are plethora of diseases like phenylketonuria, tyrosinemia, hypertryptophanemia, hyperglycinemia, cystinuria and maple syrup urine disease to name a few which are caused by the accumulation or excess of amino acids. These are in-born errors of metabolisms (IEM’s) which are caused due to the deficiency of enzymes involved in catabolic pathways of these enzymes. Hence, it is very pertinent to understand the fate of these excess amino acids in the body and their self-assembling behaviour at molecular level. From the previous literature reports it may be surmised that the single amino acids like Phenylalanine, Tyrosine, Tryptophan, Cysteine and Methionine assemble to amyloid like structures, and hence have important implications in the pathophysiology of IEM’s like phenylketonuria, tyrosinemia, hypertryptophanemia, cystinuria and hypermethioninemia respectively. In this manuscript we report the self-assembly of lysine hydrocholride to fiber like structures in deionized water. It could be observed that lysine assemble to globular structures in fresh condition and then gradually changes to fiber like morphologies by self-association over time after 24 hours. These fibers gradually change to tubular morphologies after 3 day followed by fractal irregular morphologies in 10 and 15 days respectively. Notably, lysine exists as positively charged amino acid at physiological pH and the amine groups in lysine remain protonated. Hence, the self-assembling properties of lysine hydrochloride in deionized water is also pertinent and give insights into the fate of this amino acid in body in case it remains unmetabolized. Further, MTT assays were done to analyse the toxicities of these aggregates and the assay suggest their cytotoxic nature on SHSY5Y neural cell lines. Hence, the aggregation of lysine may be attributed to the pathological symptoms caused in diseases like hyperlysinemia which is associated with the neurological problems like seizures and short-term memory as observed in case of amyloid diseases like Parkinson’s and Alzheimer’s to name a few.

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Amyloid like Aggregates Formed by the Self-Assembly of Proline and Hydroxyproline

10.26434/chemrxiv.13615385 ◽

2021 ◽

Author(s):

Bharti Koshti ◽

Ramesh, Singh ◽

Vivekshinh Kshtriya ◽

Shanka Walia ◽

Dhiraj Bhatia ◽

...

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Self Assembly ◽

Metabolic Disorders ◽

Research Work ◽

Single Amino Acid ◽

Dependent Manner ◽

Force Microscopy ◽

Aggregation Behaviour ◽

Significant Research

Single amino acid based self-assembled structures have gained a lot of interest recently owing to their pathological significance in metabolite disorders. There is plethora of significant research work which illustrate amyloid like characteristics of assemblies formed by aggregation of single amino acids like Phenylalanine, Tyrosine, Tryptophan, Cysteine and Methionine and its implications in pathophysiology of single amino acid metabolic disorders like phenylketonuria, tyrosinemia, hypertryptophanemia, cystinuria and hypermethioninemia respectively. Hence, studying aggregation behaviour of single amino acids is very crucial to assess the underlying molecular mechanism behind metabolic disorders. In this manuscript we report for the very first time the aggregation properties of non-aromatic single amino acids Hydroxy-proline and Proline. The morphologies of these were studied extensively by Optical microscopy (OM), ThT binding fluorescence microscopy, Scanning Electron Microscopy (SEM) and Atomic force microscopy (AFM). It can be assessed that these amino acids form globular structures at lower concentrations and gradually changes to tape like structures on increasing the concentration as assessed by AFM. ThT and CR binding assay reveal the aggregates do have amyloid like characteristics. Further MTT assays on SHSY5Y neural cell lines reveal cytotoxicity and the aggregates caused significant cell death in dose dependent manner. These results have important implications in understanding the pathophysiology of single amino acid disorders like Hyperprolinemia and Hydroxyprolinemia in association with amyloid diseases. The symptoms of these diseases are also accompanied by extensive neurological problems like intellectual disability, seizures and psychiatric problems which further evince amyloid like etiology for these rare in-born errors of metabolism.

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Modulation of supramolecular self-assembly of an antimicrobial designer peptide by single amino acid substitution: implications on peptide activity

Nanoscale Advances ◽

10.1039/c9na00498j ◽

2019 ◽

Vol 1 (12) ◽

pp. 4679-4682 ◽

Cited By ~ 5

Author(s):

Zhou Ye ◽

Conrado Aparicio

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Antimicrobial Peptide ◽

Amino Acid Substitution ◽

Self Assembly ◽

Single Amino Acid Substitution ◽

Single Amino Acid ◽

Hydrophobic Amino Acids ◽

Assembly Performance

Single amino acid substitution of charged or hydrophobic amino acids of a designer antimicrobial peptide modulated structural and self-assembly performance and potency.

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Unusual Aggregation Properties of Single Amino Acid L-Lysine Hydrochloride

10.26434/chemrxiv.14152976.v1 ◽

2021 ◽

Author(s):

Bharti Koshti ◽

Ramesh Singh ◽

Vivekshinh Kshtriya ◽

Shanka Walia ◽

Dhiraj Bhatia ◽

...

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Self Assembly ◽

Short Term Memory ◽

Deionized Water ◽

The Body ◽

The Self ◽

Single Amino Acid ◽

Maple Syrup ◽

Self Assembling

. The self-assembly of single amino acids is very important topic of research since there are plethora of diseases like phenylketonuria, tyrosinemia, hypertryptophanemia, hyperglycinemia, cystinuria and maple syrup urine disease to name a few which are caused by the accumulation or excess of amino acids. These are in-born errors of metabolisms (IEM’s) which are caused due to the deficiency of enzymes involved in catabolic pathways of these enzymes. Hence, it is very pertinent to understand the fate of these excess amino acids in the body and their self-assembling behaviour at molecular level. From the previous literature reports it may be surmised that the single amino acids like Phenylalanine, Tyrosine, Tryptophan, Cysteine and Methionine assemble to amyloid like structures, and hence have important implications in the pathophysiology of IEM’s like phenylketonuria, tyrosinemia, hypertryptophanemia, cystinuria and hypermethioninemia respectively. In this manuscript we report the self-assembly of lysine hydrocholride to fiber like structures in deionized water. It could be observed that lysine assemble to globular structures in fresh condition and then gradually changes to fiber like morphologies by self-association over time after 24 hours. These fibers gradually change to tubular morphologies after 3 day followed by fractal irregular morphologies in 10 and 15 days respectively. Notably, lysine exists as positively charged amino acid at physiological pH and the amine groups in lysine remain protonated. Hence, the self-assembling properties of lysine hydrochloride in deionized water is also pertinent and give insights into the fate of this amino acid in body in case it remains unmetabolized. Further, MTT assays were done to analyse the toxicities of these aggregates and the assay suggest their cytotoxic nature on SHSY5Y neural cell lines. Hence, the aggregation of lysine may be attributed to the pathological symptoms caused in diseases like hyperlysinemia which is associated with the neurological problems like seizures and short-term memory as observed in case of amyloid diseases like Parkinson’s and Alzheimer’s to name a few.

Download Full-text

Amyloid like Aggregates Formed by the Self-Assembly of Proline and Hydroxyproline

10.26434/chemrxiv.13615385.v1 ◽

2021 ◽

Author(s):

Bharti Koshti ◽

Ramesh, Singh ◽

Vivekshinh Kshtriya ◽

Shanka Walia ◽

Dhiraj Bhatia ◽

...

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Self Assembly ◽

Metabolic Disorders ◽

Research Work ◽

Single Amino Acid ◽

Dependent Manner ◽

Force Microscopy ◽

Aggregation Behaviour ◽

Significant Research

Single amino acid based self-assembled structures have gained a lot of interest recently owing to their pathological significance in metabolite disorders. There is plethora of significant research work which illustrate amyloid like characteristics of assemblies formed by aggregation of single amino acids like Phenylalanine, Tyrosine, Tryptophan, Cysteine and Methionine and its implications in pathophysiology of single amino acid metabolic disorders like phenylketonuria, tyrosinemia, hypertryptophanemia, cystinuria and hypermethioninemia respectively. Hence, studying aggregation behaviour of single amino acids is very crucial to assess the underlying molecular mechanism behind metabolic disorders. In this manuscript we report for the very first time the aggregation properties of non-aromatic single amino acids Hydroxy-proline and Proline. The morphologies of these were studied extensively by Optical microscopy (OM), ThT binding fluorescence microscopy, Scanning Electron Microscopy (SEM) and Atomic force microscopy (AFM). It can be assessed that these amino acids form globular structures at lower concentrations and gradually changes to tape like structures on increasing the concentration as assessed by AFM. ThT and CR binding assay reveal the aggregates do have amyloid like characteristics. Further MTT assays on SHSY5Y neural cell lines reveal cytotoxicity and the aggregates caused significant cell death in dose dependent manner. These results have important implications in understanding the pathophysiology of single amino acid disorders like Hyperprolinemia and Hydroxyprolinemia in association with amyloid diseases. The symptoms of these diseases are also accompanied by extensive neurological problems like intellectual disability, seizures and psychiatric problems which further evince amyloid like etiology for these rare in-born errors of metabolism.

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SAPdb: A database of nanostructures formed by self-assembly of short peptides

10.1101/685149 ◽

2019 ◽

Author(s):

Deepika Mathur ◽

Harpreet Kaur ◽

Anjali Dhall ◽

Neelam Sharma ◽

Gajendra P. S. Raghava

Keyword(s):

Amino Acids ◽

Self Assembly ◽

Aromatic Amino Acids ◽

The Self ◽

Single Amino Acid ◽

Short Peptides ◽

Experimental Conditions ◽

Surface Receptors ◽

Self Assembling ◽

Comprehensive Information

AbstractBackgroundNanostructures generated by self-assembly of peptides yield nanomaterial that has many therapeutic applications, including drug delivery and biomedical engineering, due to their low cytotoxicity and higher uptake by targeted cells owing to their high affinity and specificity towards cell surface receptors. Despite the promising implications of this rapidly expanding field, there is no dedicated resource to study peptide nanostructures.ResultThis study endeavours to create a dedicated repository of short peptides, which may prove to be the best models to study ordered nanostructures formed by peptide self-assembly. SAPdb has a repertoire of 1,049 entries of experimentally validated nanostructures formed by the self-assembling of small peptides. It includes 701 entries are of dipeptides, 328 entries belong to tripeptides, and 20 entries of single amino acid with some conjugated partners. Each entry encompasses comprehensive information about the peptide such as chemical modifications in the peptide sequences, the type of nanostructure formed, and experimental conditions like pH, temperature, and solvent required for the self-assembly of the peptide, etc. Further, our analysis has shown that the occurrence of aromatic amino acids favours the formation of self-assembling nanostructures, as indicated by a large number of entries in SAPdb contain aromatics amino acids. Besides, we have observed that these peptides form different nanostructures under different experimental conditions. SAPdb provides this comprehensive information in a hassle-free tabulated manner at a glance. User-friendly browsing, searching, and analysis modules are integrated for easy retrieval and comparison of data and examination of properties. We anticipate SAPdb to be a valuable repository for researchers engaged in the burgeoning arena of nanobiotechnology.AvailabilityThe database can be accessed on the web at https://webs.iiitd.edu.in/raghava/sapdb.

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