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Oct 28, 2022 15:05
1 yr ago
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English term
Putative sequence liability analysis
English to Russian
Law/Patents
Biology (-tech,-chem,micro-)
Конструирование антител
Putative sequence liability analysis
Potential sequence liabilities in CDRs (identified under Chothia) of the 16B8.C8 and 9F11.B7 antibodies were examined.
The following potential liabilities were considered:
M (potential oxidation site); NG, NS and NT sequence motif (potential deamidation site); DG, DS and DT sequence motif (potential isomerization site); DP sequence motif (potential site for chemical hydrolysis).
Из другого источника:
Antibody sequence liabilities and assets include:
Likely sequencing errors (eg. poor quality sequences)
Premature STOP codons or frameshift mutations
Sequence motifs that may reduce the conformational stability or might otherwise impair the functioning of antibody products
Liabilities will be shown as annotations on sequences and an overall "Score" will be given based on how many liabilities were found. Each liability adds a negative value to the overall score of a sequence*
https://help.geneiousbiologics.com/hc/en-us/articles/5324606...
Sequence Liability Identification Service
Post-translational modifications (PTMs) of antibody have the potential to affect affinity, stability, potency and homogeneity of an antibody, and this will result in complicated process in downstream development. The bioactivity and production of various isoforms of the product will be impacted. PTMs normally include deamidation, isomerization, oxidation, glycosylation, free thiol, pyro-Glutamate, C-terminal Lysine etc.
To identify the sequences within antibody variable regions, Creative Biolabs has developed algorithms to offer this kind of service to improve the potential product quality. We are dedicated to helping our clients to make smarter decisions about eliminating the program earlier in the antibody engineering process or selecting the liability free antibodies for further development. We aim to provide critical insight into your project and reduce your cost via foreseeing potential quality risks.
https://www.creative-biolabs.com/immuno-oncology/sequence-li...
Это анализ каких-то предполагаемых уязвимых сайтов/участков в последовательностях антител? (в мультитране встречал перевод участок ответственности последовательности, но как-то не отражает он сути термина)
Potential sequence liabilities in CDRs (identified under Chothia) of the 16B8.C8 and 9F11.B7 antibodies were examined.
The following potential liabilities were considered:
M (potential oxidation site); NG, NS and NT sequence motif (potential deamidation site); DG, DS and DT sequence motif (potential isomerization site); DP sequence motif (potential site for chemical hydrolysis).
Из другого источника:
Antibody sequence liabilities and assets include:
Likely sequencing errors (eg. poor quality sequences)
Premature STOP codons or frameshift mutations
Sequence motifs that may reduce the conformational stability or might otherwise impair the functioning of antibody products
Liabilities will be shown as annotations on sequences and an overall "Score" will be given based on how many liabilities were found. Each liability adds a negative value to the overall score of a sequence*
https://help.geneiousbiologics.com/hc/en-us/articles/5324606...
Sequence Liability Identification Service
Post-translational modifications (PTMs) of antibody have the potential to affect affinity, stability, potency and homogeneity of an antibody, and this will result in complicated process in downstream development. The bioactivity and production of various isoforms of the product will be impacted. PTMs normally include deamidation, isomerization, oxidation, glycosylation, free thiol, pyro-Glutamate, C-terminal Lysine etc.
To identify the sequences within antibody variable regions, Creative Biolabs has developed algorithms to offer this kind of service to improve the potential product quality. We are dedicated to helping our clients to make smarter decisions about eliminating the program earlier in the antibody engineering process or selecting the liability free antibodies for further development. We aim to provide critical insight into your project and reduce your cost via foreseeing potential quality risks.
https://www.creative-biolabs.com/immuno-oncology/sequence-li...
Это анализ каких-то предполагаемых уязвимых сайтов/участков в последовательностях антител? (в мультитране встречал перевод участок ответственности последовательности, но как-то не отражает он сути термина)
Discussion
https://www.novusbio.com/antibody-news/antibodies/characteri...
(первый абзац)
https://carterra-bio.com/resources/develop-high-quality-ther...
в транскрипте этого видео есть раздел How do we make this library?
Плюс определение для liability в Оксфордском словаре:
https://www.oxfordlearnersdictionaries.com/definition/englis...
a person or thing that causes you a lot of problems
В общем, можно выбирать из предложенных вариантов, включая последний от Игоря, что-то типа "анализ (скрининг) последовательности на потенциальные (предположительные) участки, подверженные неблагоприятным (вредным) модификациям. Про модификации говорить вполне уместно, поскольку в исходнике речь идет именно о химической стабильности, связанной с модификациями цепи.
Или же, как более общий термин, Анализ (присутствия) потенциальных участков неблагоприятных модификаций в последовательности / Анализ последовательностей на присутствие потенциальных участков неблагоприятных модификаций.
В принципе можно использовать и Ваш вариант, "потенциальные участки (но не сайты) уязвимости последовательности". О чем именно идет речь понятно из представленного контекста. В целом хотел бы обратить внимание на мою 2-ю ссылку - Biophysics for Therapeutic Protein Development. Там есть более общий раздел на стр. 132
6.4 Typical Protein Liabilities
Macromolecules in general and proteins in particular are highly complex in their
structure and have various instabilities. These protein instabilities can be broadly
classifi ed as physical or chemical instabilities (Table 6.1 ). Typical physical liabilities that should be screened for in an early assessment strategy are those
intrinsic stability parameters that can be used to predict overall stability and
aggregation propensity and undesirable solution properties, such as solubility,
high viscosity, phase separation, and opalescence. Chemical instabilities that
should be screened for include deamidation, fragmentation, and oxidation propensity (Chan and Carter 2010 ).
Т.е., liability в применении к белкам - это аналог нестабильности. Т.е., можно вместо уязвимости использовать нестабильность, что более понятно биохимикам.
Potential sequence liabilities in CDRs (identified under Chothia) of the 16B8.C8 and 9F11.B7 antibodies were examined. The following potential liabilities were considered: M (potential oxidation site); NG, NS and NT sequence motif (potential deamidation site); DG, DS and DT sequence motif (potential isomerization site); DP sequence motif (potential site for chemical hydrolysis). The results are summarized in Table 16.
В конце важна фраза: [0632] Variants of these antibodies were designed to remove the putative sequence liability motifs.
https://patentscope.wipo.int/search/en/detail.jsf?docId=WO20...
Это именно то, что описывается в приведенной вами ссылке https://www.benchling.com/blog/introducing-new-antibody-prop...
Identify Sequence Liability Sites
Пытаюсь понять, это что-то типа Анализа потенциальных участков/сайтов уязвимости последовательности? То есть не просто модификации, а негативно влияющие на свойства Ат.
Certain post-translational modifications (PTMs) on antibodies are considered “sequence liability sites,” and can impact an antibody’s stability and ability to bind antigens.
https://www.benchling.com/blog/introducing-new-antibody-prop...
https://books.google.ru/books?id=bVBDAAAAQBAJ&printsec=front...
page136
6.6.2 Chemical Stability
https://www.benchling.com/blog/introducing-new-antibody-prop...
Identify Sequence Liability Sites
см. Thesaurus
liability - the quality of being something that holds you back
bad, badness - that which is below standard or expectations as of ethics or decency; "take the bad with the good"
weak point - an attribute that is inadequate or deficient
disadvantage - the quality of having an inferior or less favorable position
https://www.thefreedictionary.com/liability
в противоположность assets (достоинствам, преимуществам) во второй ссылке