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Message: fopen(/var/lib/php/sessions/ci_session3gak8b8d4d8lc530ek6vmf48cajd0fl9): Failed to open stream: No space left on device
Filename: drivers/Session_files_driver.php
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File: /var/www/html/index.php
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Function: require_once
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Filename: Session/Session.php
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File: /var/www/html/index.php
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Function: require_once
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Message: Undefined array key "choices"
Filename: controllers/Detail.php
Line Number: 249
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File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler
File: /var/www/html/index.php
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Function: require_once
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Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 249
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File: /var/www/html/application/controllers/Detail.php
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Function: _error_handler
File: /var/www/html/index.php
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Function: require_once
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Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler
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Function: require_once
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Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 249
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File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler
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Message: strpos(): Passing null to parameter #1 ($haystack) of type string is deprecated
Filename: models/Detail_model.php
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Function: strpos
File: /var/www/html/application/controllers/Detail.php
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Function: insertAPISummary
File: /var/www/html/index.php
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Function: require_once
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Filename: helpers/my_audit_helper.php
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File: /var/www/html/application/helpers/my_audit_helper.php
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Function: str_replace
File: /var/www/html/application/controllers/Detail.php
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Function: formatAIDetailSummary
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Function: require_once
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Filename: controllers/Detail.php
Line Number: 256
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Line: 256
Function: _error_handler
File: /var/www/html/index.php
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Function: require_once
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Filename: controllers/Detail.php
Line Number: 256
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Line: 256
Function: _error_handler
File: /var/www/html/index.php
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Function: require_once
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Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
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Function: _error_handler
File: /var/www/html/index.php
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Message: Undefined array key "usage"
Filename: controllers/Detail.php
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Backtrace:
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Function: _error_handler
File: /var/www/html/index.php
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Function: require_once
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Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
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Function: _error_handler
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Message: Undefined array key "usage"
Filename: controllers/Detail.php
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Line: 258
Function: _error_handler
File: /var/www/html/index.php
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Filename: controllers/Detail.php
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Filename: controllers/Detail.php
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Filename: controllers/Detail.php
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Filename: controllers/Detail.php
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Filename: controllers/Detail.php
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Filename: controllers/Detail.php
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Function: _error_handler
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Message: file_get_contents(https://...@gmail.com&api_key=61f08fa0b96a73de8c900d749fcb997acc09): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
Filename: helpers/my_audit_helper.php
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File: /var/www/html/application/helpers/my_audit_helper.php
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Function: file_get_contents
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Function: GetPubMedArticleOutput_2016
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Function: pubMedSearch_Global
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Function: pubMedGetRelatedKeyword
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Function: require_once
Systematic N-methylated derivatives of the melanocortin receptor ligand, SHU9119, lead to multiple binding and functional selectivity toward melanocortin receptors. However, the relationship between N-methylation-induced conformational changes in the peptide backbone and side chains and melanocortin receptor selectivity is still unknown. We conducted comprehensive conformational studies in solution of two selective antagonists of the third isoform of the melanocortin receptor (hMC3R), namely, Ac-Nle-c[Asp-NMe-His-d-Nal(2')-NMe-Arg-Trp-Lys]-NH (15) and Ac-Nle-c[Asp-His-d-Nal(2')-NMe-Arg-NMe-Trp-NMe-Lys]-NH (17). It is known that the pharmacophore (His-DNal-Arg-Trp) of the SHU-9119 peptides occupies a β II-turn-like region with the turn centered about DNal-Arg. The analogues with hMC3R selectivity showed distinct differences in the spatial arrangement of the Trp side chains. In addition to our NMR studies, we also carried out molecular-level interaction studies of these two peptides at the homology model of hMC3R. Earlier chimeric human melanocortin 3 receptor studies revealed insights regarding the binding and functional sites of hMC3R selectivity. Upon docking of peptides 15 and 17 to the binding pocket of hMC3R, it was revealed that Arg and Trp side chains are involved in a majority of the interactions with the receptor. While Arg forms polar contacts with D154 and D158 of hMC3R, Trp utilizes π-π stacking interactions with F295 and F298, located on the transmembrane domain of hMC3R. It is hypothesized that as the frequency of Trp-hMC3R interactions decrease, antagonistic activity increases. The absence of any interactions of the N-methyl groups with hMC3R suggests that their primary function is to modulate backbone conformations of the ligands.
Download full-text PDF |
Source |
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5999403 | PMC |
http://dx.doi.org/10.1021/acs.biochem.7b00407 | DOI Listing |
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