2000
DOI: 10.1002/1099-1352(200007/08)13:4<167::aid-jmr502>3.3.co;2-0
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Engineered protein scaffolds for molecular recognition

Abstract: The use of so-called protein scaffolds has recently attracted considerable attention in biochemistry in the context of generating novel types of ligand receptors for various applications in research and medicine. This development started with the notion that immunoglobulins owe their function to the composition of a conserved framework region and a spatially well-defined antigen-binding site made of peptide segments that are hypervariable both in sequence and in conformation. After the application of antibody … Show more

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Cited by 46 publications
(63 citation statements)
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“…29 For thermodynamic reasons, an optimal binding site for a given ligand should not only exhibit perfect shape complementarity but also be rigid so as to minimize the loss of conformational entropy upon complex formation. This aspect has been well recognized in the field of peptide ligand selection, where various strategies have been used in order to constrain backbone flexibility.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…29 For thermodynamic reasons, an optimal binding site for a given ligand should not only exhibit perfect shape complementarity but also be rigid so as to minimize the loss of conformational entropy upon complex formation. This aspect has been well recognized in the field of peptide ligand selection, where various strategies have been used in order to constrain backbone flexibility.…”
Section: Discussionmentioning
confidence: 99%
“…18,19 The other target system MDM2 (also termed HDM2 in humans) negatively regulates the powerful tumor suppressor p53 20 through a feedback mechanism. 21 There are two possible mechanisms by which MDM2 binding can regulate p53 activity-either by 22 inhibition of the transcriptional activity of p53 or by degradation of p53 via the ubiquitin-proteasome pathway, both of which are mediated via an interaction with the Nterminal domain of p53 (residues [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29]. Activation of p53 in tumor cells, by inhibition of its physical interaction with MDM2, is a desirable point for drug intervention, as validated with the nutlin series of compounds.…”
Section: Introductionmentioning
confidence: 99%
“…Candidates for suitable protein scaffolds ought to exhibit a compact and structurally rigid core that is able to present surface loops of varying sequence and length or to otherwise tolerate side chain replacements in a contiguous surface region, including exposed hydrophobic residues, without significant changes in their folding properties [6 ]. Usually, a combinatorial library of a chosen protein scaffold is created by selective random mutagenesis of appropriate exposed surface residues [1], followed by selection of variants with the desired binding activity using well-established techniques, most predominantly phage display and related methods [7,8 ].…”
Section: The 'Scaffold' Idea: Evolution and Consolidationmentioning
confidence: 99%
“…Among the inhibitors tested, libraries of bovine pancreatic trypsin inhibitor, Alzheimer's amyloid b-protein precursor inhibitor, human lipoprotein-associated coagulation inhibitor and human pancreatic secretory trypsin inhibitor were studied early on (summarized, e.g. in [6]). More recent examples include the leech-derived trypsin inhibitor (LDTI) [63,64], the mustard trypsin inhibitor II (MTI II) [65,66] and ecotin [67 ].…”
Section: Protease Inhibitorsmentioning
confidence: 99%
“…Owing to length restrictions, we will focus on the most recent advances and publications in the field; older studies are mentioned for completeness only if they are not referenced by the more recent studies. For earlier references, the reader is directed to earlier reviews [6][7][8].…”
Section: Introductionmentioning
confidence: 99%