6 research outputs found
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Self-assembly of minimal peptoid sequences
Peptoids are biofunctional N-substituted glycine peptidomimics. Their self-assembly is of fundamental interest because they demonstrate alternatives to conventional peptide structures based on backbone chirality and beta-sheet hydrogen bonding. The search for self-assembling, water-soluble āminimalā sequences, be they peptide or peptidomimic, is a further challenge. Such sequences are highly desired for their compatibility with biomacromolecules and convenient synthesis for broader application. We report the self-assembly of a set of trimeric, water-soluble Ī±-peptoids that exhibit a relatively low critical aggregation concentration (CAC ā¼ 0.3 wt %). Cryo-EM and angle-resolved DLS show different sequence-dependent morphologies, namely uniform ca. 6 nm wide nanofibers, sheets, and clusters of globular assemblies. Absorbance and fluorescence spectroscopies indicate unique phenyl environments for Ļ-interactions in the highly ordered nanofibers. Assembly of our peptoids takes place when the sequences are fully ionized, representing a departure from superficially similar amyloid-type hydrogen-bonded peptide nanostructures and expanding the horizons of assembly for sequence-specific bio- and biomimetic macromolecules
Surface design for immobilization of an antimicrobial peptide mimic for efficient antiābiofouling
Microbial surface attachment negatively impacts a wide range of devices from water purification membranes to biomedical implants. Mimics of antimicrobial peptides (AMPs) constituted from poly(Nāsubstituted glycine) "peptoids" are of great interest as they resist proteolysis and can inhibit a wide spectrum of microbes. We investigate how terminal modification of a peptoid AMPāmimic and its surface immobilization affect antimicrobial activity. We also demonstrate a convenient surface modification scheme for enabling alkyneāazide "click" coupling on aminoāfunctionalized surfaces. Our results verified that the Nā and Cāterminal peptoid structures are not required for antimicrobial activity. Moreover, our peptoid immobilization density and choice of PEG tether resulted in a "volumetric" spatial separation between AMPs that, compared to past studies, enabled the highest AMP surface activity relative to bacterial attachment. Our analysis suggests the importance of spatial flexibility for membrane activity and that AMP separation may be a controlling parameter for optimizing surface antiābiofouling
Correction to "self-assembly of minimal peptoid sequences"
It has come to our attention that some of our cryo-electron microscopy (cryo-EM) images actually show ice contamination, (1) instead of the soft matter aggregates originally indicated in our publication. The images only relate to counterexample peptoid sequences that did not properly assemble (originally Figures 3DāK and S5EāG, IāM, and P). As such, our main finding of an ultrashort water-soluble tripeptoid assembling into ordered nanofibers is not changed. Our overall conclusions based on complementary cryo-EM, DLS, CAC, and fluorescence spectroscopy measurements are also unaffected. Nonetheless, the figures indicated and associated text require correction. In re-examining our cryo-EM data set, we found micrographs showing additional structures that are unlikely to be contaminants, which we previously took as less representative. Like the artifacts, the structures now identified are also irregular and consist of an ensemble of sizes centered around a mean. Incidentally, the mean sizes of these structures (50ā250 nm in diameter, depending on sequence) fit better with our complementary DLS resultsāno agglomeration effect of individual 5ā20 nm ice artifacts is needed anymore to reconcile the sizes measured by EM and DLS
A novel homozygous mutation in POLR3A gene causing 4H syndrome: a case report
Abstract Background 4H syndrome is a congenital hypomyelinating leukodystrophy characterized by hypodontia, hypomyelination and hypogonadotropic hypogonadism belonging to the Pol III-related leukodystrophies which arise due to mutations in the POLR3A or POLR3B gene. The clinical presentation is of neurodevelopmental delay or regression with ataxia, dystonia, nystagmus, delayed deciduous dentition and abnormal order of eruption of teeth. MRI brain shows a characteristic hypomyelination pattern. Several mutations have been described in the implicated genes but there are no reports on mutations seen in patients from India. Case presentation We report a 1Ā½Ā year old girl, only child of a non-consanguinous couple who presented with delayed developmental milestones and delayed dentition. On physical examination she had downward slanting palpebral fissures, low set ears, smooth philtrum, hypodontia, prominent body hair and clitoromegaly. There was prominent horizontal nystagmus, hypertonia of both upper and lower limbs, exaggerated deep tendon jerks and flexor planter response. She had not attained complete head control and required support to sit. She showed absent waves on brainstem evoked response audiometry and her fundus examination showed bilateral optic atrophy with prolongation of P100 latencies on visual evoked potentials. MRI Brain showed hyperintensity of entire white matter with involvement of the internal and external capsule, frontal deep white matter and corpus callosum. Her karyotype was 46 XX and her endocrinal profile was unremarkable. Clinical exome sequencing identified an unreported mutation in the POLR3A gene. The same mutation was identified by Sanger sequencing in heterozygous state in both parents. The child is being managed with physiotherapy and developmental therapy. She has been provided with hearing aids and started on speech therapy. Parents were provided anticipatory guidance and genetic counselling about autosomal recessive nature of inheritance, risk of recurrence and need for follow-up. Conclusion 4H syndrome is a rare congenital hypomyelinating leukodystrophy inherited as an autosomal recessive disorder due to mutations in the POLR3A and POLR3B gene. Delay or regression of milestones, abnormalities in dentition and endocrinal perturbations are its hallmark. A novel mutation in the POLR3A gene resulting in amino acid substitution of arginine for glutamine at codon 808 (p.R808Q) was detected in exon 18 in our case
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Surface Design for Immobilization of an Antimicrobial Peptide Mimic for Efficient Anti-Biofouling.
Microbial surface attachment negatively impacts a wide range of devices from water purification membranes to biomedical implants. Mimics of antimicrobial peptides (AMPs) constituted from poly(N-substituted glycine) "peptoids" are of great interest as they resist proteolysis and can inhibit a wide spectrum of microbes. We investigate how terminal modification of a peptoid AMP-mimic and its surface immobilization affect antimicrobial activity. We also demonstrate a convenient surface modification strategy for enabling alkyne-azide "click" coupling on amino-functionalized surfaces. Our results verified that the N- and C-terminal peptoid structures are not required for antimicrobial activity. Moreover, our peptoid immobilization density and choice of PEG tether resulted in a "volumetric" spatial separation between AMPs that, compared to past studies, enabled the highest AMP surface activity relative to bacterial attachment. Our analysis suggests the importance of spatial flexibility for membrane activity and that AMP separation may be a controlling parameter for optimizing surface anti-biofouling