![]() ![]() In particular aspects, the amino acid residue is histidine, serine, threonine, tryptophan, tyrosine, lysine or cysteine. In certain aspects, the ncAA has the ability to crosslink with an amino acid residue of said antibody. In some aspects, the affinity compound is further defined as an antibody-binding compound comprising a proximity reaction motif. In certain aspects, obtaining the affinity compound is produced by solid-phase synthesis or recombinant expression. In some aspects, the RNA is an RNA aptamer. In some aspects, the affinity compound is a small molecule, DNA, RNA, peptide, protein or a derivative thereof. In some aspects, the proximity-reactive motif comprises a non-canonical amino acid (ncAA). In a first embodiment, the present disclosure provides methods for proximity-induced site-specific conjugation of a target agent to an antibody comprising providing an affinity compound having a proximity-reactive motif, wherein the affinity compound is conjugated to the target agent and bringing the affinity compound into proximity of the antibody for a sufficient period of time to covalently link the affinity compound to said antibody. Thus, there is an unmet need for a new platform for rapid, efficient, site-specific labeling of antibodies. However, the site-specific installation of a bioorthogonal functionality requires a certain amount of antibody engineering, which is time-consuming, expensive, and may result in low yield. In general, current site-specific antibody-labeling methods first require the site-specific introduction of a unique reactive moiety into antibodies, followed by selective modification using bioorthogonal chemistry. These include THIOMAB™, which affords ultra-reactive cysteine residues for conjugation SMARTag™, which genetically encodes a peptide tag for further enzymatic modification and the SiteClick™ labeling system, which introduces an unnatural sugar and noncanonical amino acid (ncAA) technology that enables site-specific incorporation of the 21st amino acid with a distinct reactive moiety. With advances in the fields of bioorthogonal chemistry and protein engineering, several strategies have been developed for preparing site-specific antibody conjugates. Antibodies derived from such heterogeneous modification may suffer from diminished binding affinity and therapeutic index due to a lack of control over the modification ratio and site. The resulting products are heterogeneous antibody conjugates that cannot be further purified. To covalently label antibodies, various methods have been developed, most commonly involving nonspecific acylation of lysine residues with highly reactive esters and alkylation of cysteine residues with maleimides. These applications often require the modification of antibodies by various chemical molecules (e.g., fluorophores, drugs, nanoparticles) or biological reagents (e.g., enzymes, cytokines, antibodies). Monoclonal antibodies with excellent selectivity and a broad collection of targets are extensively used as affinity reagents in many biological applications, from in vitro assays to disease diagnostics to targeted therapies. More particularly, it concerns methods of conjugating agent(s) to an antibody. The disclosure relates generally to the field of molecular biology. The sequence listing that is contained in the file named “RICEP044WO.txt”, which is 3.35 KB (as measured in Microsoft Windows) and was created on May 10, 2019, is filed herewith by electronic submission and is incorporated by reference herein. 62/670,675, filed May 11, 2018, which is incorporated herein by reference in its entirety. They resumed stamping the date code on the barrel on 10/1/01.This application claims the benefit of U.S. They continued to mark the date code on the end flap of the shipping box. On 8/9/99, stopped stamping the barrels with the date code. One needs to be sure that the barrel is original to the gun before trusting the Barrel Code listing, above. Using these barrel codes to date a shotgun is somewhat unreliable, as shotgun barrels are often interchanged at random. Using barrel codes (such as those listed above) to date the manufacture are reliable on Remington rifles, as the company rarely changed barrels on a customer’s rifle. Serial Numbers by date (factory record book)Ī few other serial lists… NO A LOT LOOK HERE! B – Jan ![]() – K – P – O – W – D – E – R – X Barrel Code Location Diagram Months of the year, for example B=January, L= February Near the frame that identifies the year and month of Have a code located on the left side of the barrel ![]()
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