2019
DOI: 10.1002/adtp.201800143
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PDZ Domains as Drug Targets

Abstract: Protein-protein interactions within protein networks shape the human interactome, which often is promoted by specialized protein interaction modules, such as the postsynaptic density-95 (PSD-95), discs-large, zona occludens 1 (ZO-1) (PDZ) domains. PDZ domains play a role in several cellular functions, from cell-cell communication and polarization, to regulation of protein transport and protein metabolism. PDZ domain proteins are also crucial in the formation and stability of protein complexes, establishing an … Show more

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Cited by 77 publications
(97 citation statements)
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References 339 publications
(719 reference statements)
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“…These domains bind by β-strand augmentation to SLiMs that are called PBMs, most commonly known to be found in the C terminus of fully or partially disordered proteins. These interactions are widely studied and their link to various diseases and infections has been previously established ( 139 ). A PBM candidate is also found in the very C terminus of the cytosolic tail of all vertebrate ACE2 proteins ( Fig.…”
Section: Resultsmentioning
confidence: 99%
“…These domains bind by β-strand augmentation to SLiMs that are called PBMs, most commonly known to be found in the C terminus of fully or partially disordered proteins. These interactions are widely studied and their link to various diseases and infections has been previously established ( 139 ). A PBM candidate is also found in the very C terminus of the cytosolic tail of all vertebrate ACE2 proteins ( Fig.…”
Section: Resultsmentioning
confidence: 99%
“…PDZ domains are regarded as promising drug targets for neurological and oncological disorders, as well as viral infections. Many structure-guided efforts are underway towards the development of small-molecule or peptidic modulators of PDZ domains [83,84], including the PDZ domains from Shank3, a central scaffolding protein of the post-synaptic density protein complex [85] and of the protein interacting with C kinase (PICK1), a regulator of AMPA receptor trafficking at neuronal synapses [86].…”
Section: Structural Insight Into Tight-junction Proteins Their Domentioning
confidence: 99%
“…Although this approach is virtually unlimited with regard to possible peptide building blocks, this cleavage will leave peptides as terminal amides as do other commonly applied cleavage methods (Mcbride et al, 2016). Studies of PPIs that rely on interactions with C-terminal extremities, such as PDZ-domains (Christensen et al, 2019), may have to apply alternative cleavage strategies (Fraczyk et al, 2018). Here, we validated mSPOT synthesized peptides by LCMS and HPLC (Table S7) and determined the average purity of 15mers as 61 G 24% and 47 G 12% for 20mers.…”
Section: Limitations Of the Studymentioning
confidence: 99%