Statistical molecular design of peptoid libraries
Molecular DiversityPublished 1 June 1998
Anna Linusson, Svante Wold, Bo Nordén
Citations31
SJR quartileQ2
SJR score0.65
SNIP1.10
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
TL;DR
Multivariate quantitative structure-activity relationships (MQSARs) were developed relating renin inhibition to the peptoid sequences variation, parametrized by the z-scales, and the number of building block sets could be reduced from six to three.
Abstract
Statistical experimental design provides an efficient approach for selecting the building blocks to span the structural space and increase the information content in a combinatorial library. A set of renin-inhibitors, hexapeptoids, is used to illustrate the approach. Multivariate quantitative structure-activity relationships (MQSARs) were developed relating renin inhibition to the peptoid sequences variation, parametrized by the z-scales. By using the information from the models, the number of building block sets could be reduced from six to three. Using a statistical molecular design (SMD) reduces the number of compounds from more than 100,000 down to 90. A second SMD was used for comparison, based on less prior knowledge. This gave a reduction from over 2 billion to 120 compounds.
Keywords
MedicineBiochemistry, Genetics and Molecular Biology
Journal of the Royal Statistical Society Series B (Statistical Methodology)Cross-Validatory Choice and Assessment of Statistical Predictions
10,527 Citations1974M. Stone
Statistics for experimenters. An introduction to design, data analysis, and model building.
4,028 Citations1978George E. P. Box, William G. Hunter +1 more
SIAM Journal on Scientific and Statistical ComputingThe Collinearity Problem in Linear Regression. The Partial Least Squares (PLS) Approach to Generalized Inverses
2,520 Citations1984Svante Wold, Axel Ruhe +2 more
TechnometricsCross-Validatory Estimation of the Number of Components in Factor and Principal Components Models
2,496 Citations1978Svante Wold
NatureCorrelation of Biological Activity of Phenoxyacetic Acids with Hammett Substituent Constants and Partition Coefficients
1,055 Citations1962Corwin Hansch, Peyton P. Maloney +2 more
The need for an aromatic ring with at least one unsubstituted position for auxin activity confirms the original belief that an ortho position in the phenoxyacetic acids is most suitable stereoelectronically to serve as one of the two points which attach the molecule to the plant substrate.
Journal of Medicinal ChemistryNew Chemical Descriptors Relevant for the Design of Biologically Active Peptides. A Multivariate Characterization of 87 Amino Acids
698 Citations1998Maria Sandberg, Lennart Eriksson +3 more
The new extended and updated principal property scales, the z-scales, were calculated and aligned to previously reported z(old)-scales and validated by the use in quantitative sequence-activity modeling (QSAM) of 89 elastase substrate analogues and in a QSAM of 29 neurotensin analogues.
VCH eBooksChemometric methods in molecular design
560 Citations1995H. Van De Waterbeemd
Molecular concepts experimental design in synthesis-planning and structure-property correlations multivariate analysis of chemical and biological data statistical validation of QSAR results.
Journal of Medicinal ChemistryPeptide quantitative structure-activity relationships, a multivariate approach
547 Citations1987Sven Hellberg, Michael Sjoestroem +2 more
Multivariate QSARs are developed for four families of peptides, and it is shown how these QSars can predict the activity of new peptide analogues.
TechnometricsAn Algorithm for the Construction of "D-Optimal" Experimental Designs
426 Citations2000Toby J. Mitchell
Chemometrics and Intelligent Laboratory SystemsAnalysis of two partial-least-squares algorithms for multivariate calibration
348 Citations1987Rolf Manne
Two algorithms for multivariate calibration are analysed in terms of standard linear regression theory and the matrix inversion problem of linear regression is shown to be solved by transformations to a bidiagonal form in PLS1 and to a triangular form inPLS2.
Journal of Medicinal ChemistryMeasuring Diversity: Experimental Design of Combinatorial Libraries for Drug Discovery
301 Citations1995Éric Martin, Jeffrey M. Blaney +4 more
New methods to quantify molecular diversity using descriptors that characterize lipophilicity, shape and branching, chemical functionality, and specific binding features are described and quantify the overall diversity accessible to different families of combinatorial chemistry.
Journal of Chemical Information and Computer SciencesMultivariate quantitative structure-activity relationships (QSAR): conditions for their applicability
167 Citations1983Svante Wold, William J. Dunn
Quantitative Structure-Activity RelationshipsMultivariate Parametrization of 55 Coded and Non‐Coded Amino Acids
121 Citations1989Jörgen Jönsson, Lennart Eriksson +3 more
The previously derived z-scales for the 20 coded amino acids have been extended to cover non-coded amino acids to model 40 bradykinin potentiating pentapeptides, and 48 dipeptides with bitter taste.
Annual reports in medicinal chemistryChapter 33. Recent Advances in the Generation of Molecular Diversity
99 Citations1993Walter H. Moos, Grant D. Green +1 more
This chapter describes a comprehensive review of the recent advances in the field of chemically generated molecular diversity, including the combination of chemical and biological diversity techniques, used to enhance the tumor necrosis factor (TNF) activity.
Pharmaceutical ResearchRenin Inhibitors
63 Citations1987William J. Greenlee
Progress toward clinically useful inhibitors of renin, especially progress toward potent, low molecular weight inhibitors likely to become useful therapeutic agents, is reviewed.
Journal of Medicinal ChemistryAnalysis of a 29 Full Factorial Chemical Library
47 Citations1995S. Stanley Young, Douglas M. Hawkins
It is shown that analytical and visualization methods can be used synergistically to analyze a large, complex, high-dimensional data set and that a fractional factorial design of 128 compounds would give essentially the same information.
Journal of Peptide ResearchDesign of active analogues of a 15‐residue peptide using D‐optimal design, QSAR and a combinatorial search algorithm
38 Citations1997Roger P. Mee, Tim Auton +1 more
Analysis of the PLS models indicates that hydrophobicity and amphipathicity are the most important features influencing activity for this class of compound.
Publications (Konstfack University of Arts, Crafts, and Design)A multivariate approach to QSAR
27 Citations1986Sven Hellberg
Quantitative structure-activity relationships (OSAR) constitute empirical analogy models connecting chemical structure and biological activity and the analogy approach to QSAR assume that the factors ...