English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Structure-based prediction of asparagine and aspartate degradation sites in antibody variable regions.

Sydow, J. F., Lipsmeier, F., Larraillet, V., Hilger, M., Mautz, B., Mølhøj, M., et al. (2014). Structure-based prediction of asparagine and aspartate degradation sites in antibody variable regions. PLoS One, 9(6): e100736. doi:10.1371/journal.pone.0100736.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0023-CE17-D Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0027-CCE3-A
Genre: Journal Article

Files

show Files
hide Files
:
2056556.pdf (Publisher version), 2MB
Name:
2056556.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-
:
2056556_Suppl_1.tif (Supplementary material), 2MB
Name:
2056556_Suppl_1.tif
Description:
-
Visibility:
Public
MIME-Type / Checksum:
image/tiff / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-
:
2056556_Suppl_2.tif (Supplementary material), 3MB
Name:
2056556_Suppl_2.tif
Description:
-
Visibility:
Public
MIME-Type / Checksum:
image/tiff / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-
:
2056556_Suppl_3.docx (Supplementary material), 42KB
Name:
2056556_Suppl_3.docx
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/vnd.openxmlformats-officedocument.wordprocessingml.document / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-
:
2056556_Suppl_4.docx (Supplementary material), 43KB
Name:
2056556_Suppl_4.docx
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/vnd.openxmlformats-officedocument.wordprocessingml.document / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-
:
2056556_Suppl_5.docx (Supplementary material), 43KB
Name:
2056556_Suppl_5.docx
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/vnd.openxmlformats-officedocument.wordprocessingml.document / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-

Creators

show
hide
 Creators:
Sydow, J. F., Author
Lipsmeier, F., Author
Larraillet, V., Author
Hilger, M., Author
Mautz, B., Author
Mølhøj, M., Author
Kuentzer, J., Author
Klostermann, S., Author
Schoch, J., Author
Voelger, H. R., Author
Regula, J. T., Author
Cramer, P.1, Author              
Papadimitriou, A., Author
Kettenberger, H., Author
Affiliations:
1Department of Molecular Biology, MPI for Biophysical Chemistry, Max Planck Society, ou_1863498              

Content

show
hide
Free keywords: -
 Abstract: Monoclonal antibodies (mAbs) and proteins containing antibody domains are the most prevalent class of biotherapeutics in diverse indication areas. Today, established techniques such as immunization or phage display allow for an efficient generation of new mAbs. Besides functional properties, the stability of future therapeutic mAbs is a key selection criterion which is essential for the development of a drug candidate into a marketed product. Therapeutic proteins may degrade via asparagine (Asn) deamidation and aspartate (Asp) isomerization, but the factors responsible for such degradation remain poorly understood. We studied the structural properties of a large, uniform dataset of Asn and Asp residues in the variable domains of antibodies. Their structural parameters were correlated with the degradation propensities measured by mass spectrometry. We show that degradation hotspots can be characterized by their conformational flexibility, the size of the C-terminally flanking amino acid residue, and secondary structural parameters. From these results we derive an accurate in silico prediction method for the degradation propensity of both Asn and Asp residues in the complementarity-determining regions (CDRs) of mAbs.

Details

show
hide
Language(s): eng - English
 Dates: 2014-06-24
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1371/journal.pone.0100736
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: PLoS One
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: 13 Volume / Issue: 9 (6) Sequence Number: e100736 Start / End Page: - Identifier: -