MedChemComm September 2012 Front Cover Image For The "Examining The Effects Of Vitamin B12 Conjugation…" Paper

Blogging a blog post recently blogged here in a post, with a zoom-in below because no decent-sized version of the same can be found on the MedChemComm site, all pertaining to the "Examining the effects of vitamin B12 conjugation on the biological activity of insulin: a molecular dynamic and in vivo oral uptake investigation" article from Susan Clardy-James, myself, Timothy J. Fairchild and Robert P. Doyle in ChemMedComm (available at

The MedChemComm post also provides the caption for the cover (below), which I reproduce below for context:

Oral delivery of drugs aims to open up new areas of peptide/protein therapeutics associated with the removal for a need for injections. The major problems facing oral delivery of peptides/proteins is hydrolysis/proteolysis in the gastrointestinal tract and an inefficient uptake mechanism for peptides/proteins from the tract. Robert P. Doyle et al. are interested in the use of the vitamin B12 dietary uptake pathway to address these hurdles. In this paper Doyle et al. report the synthesis, purification and characterisation of a new B12-insulin conjugate attached between the B12 ribose hydroxyl group and insulin PheB1.

Gumming Up Appetite to Treat Obesity – Vitamin B12 Bioconjugate Project (& Graphic) Mention In Scientific American

From the "free press" division of the blog, a recent post by Ferris Jabr on the site highlights yet another evolutionarily fascinating application of cyanocobalamin (herein referred to as B12) out of the Rob Doyle Lab for the non-invasive delivery of small molecules into the human-person. Here, a mechanism for the delivery of human peptide YY (hPYY) into the bloodstream via a food-free mechanism (unless you count the gum flavorings as a fruit). From the thorough and accessible article (with a decent balance of sciam and non-sciam redirecting)…

CHEMICAL COUPLE: The appetite-suppressing hormone hPYY hitches a ride with vitamin B-12 from the stomach to the bloodstream (caption credit: sciam).

Losing weight is not always about anticipating swimsuit season or squeezing into skinny jeans—for the clinically obese, losing weight is about fighting serious illness and reclaiming health. But the primal part of the brain that regulates appetite will not place a moratorium on hunger just because someone and their doctor acknowledge the need to lose weight. Researchers at Syracuse University are working toward a unique solution: a stick of chewing gum that suppresses appetite.

A slightly-larger version of the image on the site is reproduced above (with the image credit most welcome on the site). For a bit more information about the general properties of B12 and its potential applications for other diet-related issues, a few articles described here @swv link to more complete discussions…

* Vitamin B12 In Drug Delivery: Breaking Through The Barriers To A B12 Bioconjugate Pharmaceutical

* The Binding Of Vitamin B12 To Transcobalamin(II); Structural Considerations For Bioconjugate Design – A Molecular Dynamics Study

* B12-Insulin Bioconjugate/Transcobalamin(II)/Insulin Receptor Cover Image For The April Issue Of Clinical Chemistry

* New B12-Insulin-TCII-Insulin Receptor Cover Image For This Month's ChemMedChem (March 2009)

* Exploring the Implications of Vitamin B12 Conjugation to Insulin on Insulin Receptor Binding and Cellular Uptake

Vitamin B12 In Drug Delivery: Breaking Through The Barriers To A B12 Bioconjugate Pharmaceutical

In press in Expert Opinion On Drug Delivery (DOI:10.1517/17425247.2011.539200). The theory section (the only part I can properly speak to) builds on the discussion section of the full theory paper in Molecular Biosystems from earlier this year, providing an outlet for some of the more speculative design possibilities for trinary B12 bioconjugate design. Given that (1) there are mechanisms for cleavage at both of the proposed positions and (2) the molecular dynamics work indicates that, at least, TCII (transcobalamin II) can easily accommodate a bi-functionalized cobalamin, the A-B12-C design possibility is probably the most interesting long-term idea to come out of the computational side of the B12-insulin bioconjugate study (or so I argue).

Having "B12" and "cobalamin" in a blog post guarantees a bunch of useless moderation-necessary comments from vita-spam sites.

Susan M. Clardy, Damian G. Allis, Timothy J. Fairchild & Robert P. Doyle

Syracuse University, Syracuse, Department of Chemistry, NY 13244-4100, USA

Importance of the field: Vitamin B12 (B12) is a rare and vital micronutrient for which mammals have developed a complex and highly efficient dietary uptake system. This uptake pathway consists of a series of proteins and receptors, and has been utilized to deliver several bioactive and/or imaging molecules from 99mTc to insulin.

Areas covered in this review: The current field of B12-based drug delivery is reviewed, including recent highlights surrounding the very pathway itself.

What the reader will gain: Despite over 30 years of work, no B12-based drug delivery conjugate has reached the market-place, hampered by issues such as limited uptake capacity, gastrointestinal degradation of the conjugate or high background uptake by healthy tissues. Variability in dose response among individuals, especially across ageing populations and slow oral uptake (several hours), has also slowed development and interest.

Take home message: This review is intended to stress again the great potential, as yet not fully realized, for B12-based therapeutics, tumor imaging and oral drug delivery. This review discusses recent reports that demonstrate that the issues noted above can be overcome and need not be seen as negating the great potential of B12 in the drug delivery field.