ChemInform Abstract: Mixture-Based Combinatorial Libraries from Small Individual Peptide Libraries: A Case Study on α-Antitrypsin Deficiency

Screening solid-phase combinatorial libraries of bioactive compounds against fluorescently labeled target biomolecules is an established technology in ligand and drug discovery. Rarely, however, do screening methods include comprehensive strategies—beyond mere library blocking and competitive screening—to ensure binding selectivity of selected leads. This work presents a method for multiplexed solid-phase peptide library screening using a ClonePix 2 Colony Picker that integrates (i) orthogonal fluorescent labeling for positive selection against a target protein and negative selection against competitor species with (ii) semi-quantitative tracking of target vs. competitor binding for every library bead. The ClonePix 2 technology enables global at-a-glance evaluation and customization of the parameters for bead selection to ensure high affinity and selectivity of the isolated leads. A case study is presented by screening a peptide library against green-labeled human immunoglobulin G (IgG) and red-labeled host cell proteins (HCPs) using ClonePix 2 to select HCP-binding ligands for flow-through chromatography applications. Using this approach, 79 peptide ligand candidates (6.6% of the total number of ligands screened) were identified as potential HCP-selective ligands, enabling a potential rate of >3,000 library beads screened per hour.

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Field Note: Introducing SYSPROP—A Software Tool to Identify Small but Economically Viable Timber Parcels in the Pacific Northwest

Journal of Forestry ◽

10.1093/jofore/fvab029 ◽

2021 ◽

Author(s):

Edward Helderop ◽

Tony H Grubesic ◽

Clayton N Edson

Keyword(s):

United States ◽

Pacific Northwest ◽

Software Tool ◽

Timber Harvest ◽

The United States ◽

Automatic Identification ◽

Small Individual ◽

The Pacific ◽

Field Note

Abstract The past several decades have seen a steady decline in timber harvest rates from many parts of the United States, particularly the Pacific Northwest. Although various factors fuel this decline, one of the principal drivers is increasing rates of parcelization of the landscape. Increasingly parcelized forested landscapes tend to be more challenging to log—both because urbanization rates are somewhat correlated with parcelization but also due to the additional administrative overhead in securing logging rights in increasingly smaller parcels. The purpose of this note is to introduce SYSPROP, a tool to aid in the automatic identification of economically viable parcels for logging. We conclude with a case study of a small logging company operating in Washington State that used this tool to identify several promising parcels. Study Implications: In the Pacific Northwest of the United States, large areas of forested landscape are being broken into small individual parcels. This makes adequately harvesting timber from these tracts of land difficult, because stumpage rights need to be negotiated for each distinct parcel. We introduce a set of software tools that allows a user to automatically identify economically viable parcels for logging company operators. The paper concludes with an exploration of a case study detailing how one small logging company used the software.

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Use of Mathematical Structural Invariants in Analyzing Combinatorial Libraries: A Case Study with Psoralen Derivatives

Current Computer - Aided Drug Design ◽

10.2174/1573409911006040240 ◽

2010 ◽

Vol 6 (4) ◽

pp. 240-251 ◽

Cited By ~ 2

Author(s):

Subhash C. Basak ◽

Denise Mills ◽

Brian D. Gute ◽

Alexandru T. Balaban ◽

Kanika Basak ◽

...

Keyword(s):

Combinatorial Libraries ◽

Psoralen Derivatives ◽

Structural Invariants

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A case study of combinatorial libraries: Endothelin receptor antagonist hexapeptides

Bioorganic & Medicinal Chemistry Letters ◽

10.1016/0960-894x(95)00349-x ◽

1995 ◽

Vol 5 (17) ◽

pp. 2041-2044 ◽

Cited By ~ 5

Author(s):

B. Neustadt ◽

A. Wu ◽

E.M. Smith ◽

T. Nechuta ◽

A. Fawzi ◽

...

Keyword(s):

Receptor Antagonist ◽

Combinatorial Libraries ◽

Endothelin Receptor Antagonist ◽

Endothelin Receptor

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Isolation of peptides from phage-displayed random peptide libraries that interact with the talin-binding domain of vinculin

Biochemical Journal ◽

10.1042/bj3240523 ◽

1997 ◽

Vol 324 (2) ◽

pp. 523-528 ◽

Cited By ~ 13

Author(s):

Nils. B ADEY ◽

Brian. K KAY

Keyword(s):

Amino Acid ◽

Sequence Similarity ◽

Combinatorial Libraries ◽

Binding Domain ◽

Peptide Libraries ◽

Biologically Relevant ◽

Random Peptide ◽

Binding Domains ◽

Random Peptide Libraries ◽

Binding Peptides

Peptides isolated from combinatorial libraries typically interact with, and thus help to characterize, biologically relevant binding domains of target proteins. To characterize the binding domains of the focal adhesion protein vinculin, vinculin-binding peptides were isolated from two phage-displayed random peptide libraries. Altogether, five non-similar vinculin-binding peptides were identified. Despite the lack of obvious sequence similarity between the peptides, binding and competition studies indicated that all five interact with the talin-binding domain of vinculin and do not disrupt the binding of α-actinin or paxillin to vinculin. The identified peptides and talin bind to vinculin in a comparable manner; both bind to immobilized vinculin, but neither binds to soluble vinculin unless the C-terminus of vinculin has been deleted. An analysis of amino acid variants of one of the peptides has revealed three non-contiguous motifs that also occur in the region of talin previously demonstrated to bind vinculin. Amino acid substitutions within a 127-residue segment of talin capable of binding vinculin confirmed the importance of two of the motifs and suggest that residues critical for binding are within a 16-residue region. This study demonstrates that the vinculin-binding peptides interact with vinculin in a biologically relevant manner and represent an excellent tool for further study of the biochemistry of vinculin.

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The Evolution of Trust in Japan

Strategic Marketing in Fragile Economic Conditions - Advances in Marketing, Customer Relationship Management, and E-Services ◽

10.4018/978-1-4666-6232-2.ch002 ◽

2014 ◽

pp. 22-42

Author(s):

Nabyla Daidj

Keyword(s):

Large Firm ◽

Organisational Structure ◽

Corporate Ownership ◽

Small Individual ◽

Car Industry ◽

Corporate Networks ◽

Industrial Organisation ◽

Main Bank

Research on corporate ownership in Japan focus mainly on corporate networks: horizontal and vertical keiretsu. Horizontal keiretsu are networks of firms whose small individual equity stakes in each other collectively sum to control blocks structured around a main bank. Vertical (manufacturing) keiretsu are similar structures that encompass the suppliers and customers of a single large firm. Vertical networks, representative of long-lasting and stable relationships (especially in the Japanese car industry), are undergoing drastic changes. Many authors insist there have been significant changes observed within keiretsu since the end of the 1990s. To have a better understanding of the evolution of trust within keiretsu, it is necessary to analyse its industrial organisation evolution. The authors first situate the Japanese organisational structure and then present a review of the main stages of the change that has affected vertical keiretsu, together with the factors that have contributed to this change. Finally, they analyse the evolution of trust within keiretsu. The authors illustrate the evolution of keiretsu via a case study: the Nissan keiretsu closely related to the Renault-Nissan alliance.

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