Dataset Information

Raising the Bar On-Bead: Efficient On-Resin Synthesis of ?-Conotoxin LvIA.

ABSTRACT: ?4/7-Conotoxin LvIA is an isoform-selective inhibitor of the ?3?2 nicotinic acetylcholine receptor. An efficient strategy for the synthesis of this toxin is critical to advancing its utility as a probe for receptor function and as a potential pharmaceutical lead target. On-resin methods for peptide synthesis offer potential synthetic advantages; however, strategies for on-resin formation of multiple disulfides have historically been low-yielding. Here, we harness the reactivity of the Allocam protecting group and employ 3-amino acid spacer strategy to synthesize ?4/7-conotoxin LvIA via three different on-resin strategies, each of which results in an isolated yield higher than prior fully on-resin approaches.

SUBMITTER: Kondasinghe TD

PROVIDER: S-EPMC6764457 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Raising the Bar On-Bead: Efficient On-Resin Synthesis of α-Conotoxin LvIA.

Kondasinghe Thilini D TD Saraha Hasina Y HY Jackowski Shane T ST Stockdill Jennifer L JL

Tetrahedron letters 20181122 1

α4/7-Conotoxin LvIA is an isoform-selective inhibitor of the α3β2 nicotinic acetylcholine receptor. An efficient strategy for the synthesis of this toxin is critical to advancing its utility as a probe for receptor function and as a potential pharmaceutical lead target. On-resin methods for peptide synthesis offer potential synthetic advantages; however, strategies for on-resin formation of multiple disulfides have historically been low-yielding. Here, we harness the reactivity of the Allocam pr ...[more]

PMID: 31564757

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Project description:ContextMedical schools seek for measures to improve their students' study progress and are responsible for a diverse student population.ObjectivesThe effect of a stricter academic dismissal (AD) policy in medical school on short-term and long-term study progress was investigated in a longitudinal cohort study. In addition, differential effects for subgroups were assessed by intersecting gender, ethnicity and prior education (intersectional framework).MethodsParticipants were first-year Bachelor students enrolled in 2011 to 2016 in a Dutch medical school. For cohorts 2011-2013, the AD policy consisted of a minimum of 67% of Year-1 credits required to remain enrolled (67%-policy, n = 1189), and for cohorts 2014-2016, this bar was raised to 100% of Year-1 credits (100%-policy, n = 1233). Outcome measures on study progress were Year-1 completion and dropout (short term) and Bachelor completion in three and four years (long term).ResultsOverall, Year-1 completion rates increased under the 100%-policy compared to the 67%-policy (OR = 2.50, 95%-CI:2.06-3.03, P < .001). Yet, this increase was not present for students with non-standard prior education - except for males with a migration background (OR = 7.19, 95%-CI:2.33-25.73, P < .01). The dropout rate doubled under the 100%-policy (OR = 2.41, 95%-CI:1.68-3.53, P < .001). Mainly students with standard prior education dropped out more often (OR = 3.68, 95%-CI:2.37-5.89, P < .001), except for males with a migration background. Bachelor completion rates after three and four years were not positively affected by the 100%-policy. Notably, females without a migration background and with non-standard prior education suffered from the 100%-policy regarding Bachelor completion after three years (OR = 0.29, 95%-CI:0.11-0.76, P < .05).ConclusionsDespite increased dropout rates, the stricter AD policy improved Year-1 completion rates - especially for under-represented subgroups, thereby improving study progress without harming student diversity on the short term. However, these positive effects did not hold regarding Bachelor completion rates indicating that long-term effects require higher performance standards throughout the Bachelor, which in turn may harm other subgroups and thereby student diversity.

Dataset Information

Raising the Bar On-Bead: Efficient On-Resin Synthesis of ?-Conotoxin LvIA.

Publications

Raising the Bar On-Bead: Efficient On-Resin Synthesis of α-Conotoxin LvIA.

Similar Datasets

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