GPCR Antibody Technology

GPCR Diagram

Generating Conformationally-Sensitive Antibodies to GPCRs

It has been difficult to obtain antibodies to GPCRs, particularly high affinity antibodies to extracellular domains. This may be due to several factors including tolerance and the relatively small amount of exposed hydrophilic surface for many GPCRs. Antibodies have been developed to short peptide sequences and linear epitopes generated as GST-fusion proteins, but these often lack sufficient affinity to compete with endogenous ligands having multiple points of contact on the receptor. Efforts to generate antibody to native proteins include the use of cells expressing the target GPCR as an immunogen or to select phage expressing anti-GPCR antibodies. These methods are limited by the low levels at which GPCRs are expressed on the surface of cells, and by the high levels of other antigenic proteins expressed by the cells. ConfometRx has developed a method of preparing antigenic proteoliposomes containing a high density of purified, native GPCRs. This approach has been used to generate conformationally-sensitive antibodies that recognize more than just a single linear epitope. This affords the antibodies higher affinity and greater selectivity.

Therapeutic Antibodies

Humanized antibodies are becoming an important class of therapeutics with excellent safety and efficacy profiles. There are tremendous commercial opportunities for new antibody therapeutics that act on GPCR targets for which there are no effective small molecule drugs, and against which others have been unable to develop peptide or antibody drugs. ConfometRx possesses the technology needed for generating highly selective, high affinity therapeutic antibodies against these targets.

Target Validation

In addition to their potential for being effective therapeutics for GPCRs, antibodies to GPCRs may prove useful in characterizing the physiology and pathophysiology of GPCRs for which no high affinity small molecular weight drugs are available. Anti-GPCR antibodies may provide insight into the consequences of disrupting the function of a particular GPCR in vivo, thereby providing the rationale for undertaking an expensive drug discovery effort.

GPCR Crystallography

Antibodies recognizing the native third intracellular loop of the human β2 adrenoceptor have recently been used to obtain a crystal structure of this GPCR in the Kobilka laboratory at Stanford.

Collaborating with ConfometRx

ConfometRx will offer its antibody technology on a contract basis to partners in the biotechnology and pharmaceutical industries. In addition to preparation of antigenic proteoliposomes containing functional GPCRs, ConfometRx can assist in developing assays for screening hybridoma and phage clones, and in the functional characterization of antibodies.

For more information, please contact us.