I came into the world of biopharmaceutical manufacturing after a career in academic. I had extensive experience with proteins and chemical modification which had been use in a previous sabbatical in a facilty devoted to plasma proteins. However, I was now in the world of cell culture without much of a guidebook. So when the term S+L- was tossed around like a tray of donuts at my first technical meeting, I was clueless. While I did get up to speed quickly, the moment stuck in my head. Now while working on the second edition of the Biochemistyr and Molecular Biology Compendium, I deicided to include an entry on S+L- and I was disappointed on how much information was available in the literature. I hope that the material here will be of value.
PEGylation of Factor VIII
Some thoughts on the various PEGylated Factor VIII products
PIPETTE OR PIPET
An interesting story - Great artcile of this from Dr. Gold at Artel
Another example from the developing Compendium and a comparison of 2007 copy and 2018 copy. One challenge here is distinguishing between macroarray and microarray in respect to element density. My sense is that macroarray mostly corresponding to a 96 well microplate with a density of approximately 4 elements per square cm. Experiemental design and data interpretation are the challenges with the microarray technologies.
This is another update on material for the second edition of the Biochemistry and Molecular Biology Compendium. A lot has happened since 2007.
I have worked with lectins on several occasions but never took the time to learn much about them other than as a tool to study glycoproteins. As I make progress with the revision of the Compendium, it is interesting to learn more about this group of proteins who share the ability to recognized carbohydrate but little else
HOX GENES AND HOX CODES
It has been many years since I took my single course in genetics but I still have the text (King, R.C., Genetics, Oxford University Press, New York, New York, USA, 1962 which has a brief mention of homeotic mutations. Much has changed the story of HOX gene is fascinating with the understanding that metazoan complexitiy is a product of more sophisticated regulation and not a greater number of genes
ENZYMES AND HETEROGENOUS CATALYSIS
As I move through the revision of the Biochemistry and Molecular Biology Compenium, I find that a lot has changed in 10 years and also that I am looking as these various subjects from a different perspecive. Heterogeneous catalysis became a lot more interesting when I spent more time considering enzymes as heterogeneous catalysts.
Ectodomain Versus Extracellular Domain
THERAPEUTIC USE OF DNAZYMES
An interesting observation on the difference between in vivo and in vitro when you depend on something beside the therapeutic agent
It has been a couple of months since I have posted an entry from the 2nd Edition of Biochemistry and Molecular Biology Compendium. I have been busy with some final work on the 5th edition of The Handbook of Biochemistry and Moleclar Biology. I also did not have an entry which I thought would be useful on the website. That said (or rather written), I introduce dark matter. As with other entries, much has changed in the decade since the first edtion
As with calcineurin, an example of copy being prepared for the 2nd editon of the Biochemistry and Molecular Biology Compendium. Commetns and corrections will be appreciated.
Another example of the material being revised for the second edition of the Bochemistry and Molecular Biology Compendium
ANTISENSE PEPTDIES - WHAT A DECADE DOES! ALSO KNOWN AS COMPLEMENTARY PEPTIDES
I continue to be intrigued by antisense peptides - also known as complementary peptides -There is quite difference between te 2007 entry and the 2017 entiry.
Antibody Entry for Compendium Revision
The Compendium for Biochemistry and Molecular Biology is being revised. I am including the antibody entry to provide an illustration of the extend of revision.
FAKE RESEARCH REAGENTS
The issue of fake research reagents is an increasing problem, The problem is of great concern with antibody reagents.
Second Edition of Biochemistry and Molecular Biology Compendium is in development
GLYCOPEGYLATION AND FACTOR VIII
The quest for a factor VIII with extended half-life goes on.
STABILITY OF ANTIBODY-DRUG CONJUGATES
Maleimide chemistry just gets more interesting and useful - Some thoughts from work intended for the 5th Edtion of the Handbook of Biochemistry and Molecular Biology
MICHAEL ADDITIONS WITH FUMARATE AS MICHAEL DONOR
I came across some old studies on the formation of conjugates between fumarate and thiols and was interested to see some interesting studies subsequent to the early observations by Baynes and coworkers.
A NOVEL ASSAY FOR PHOSPHOLIPASE A
A novel assay using a reagent obtained at local retail
MIT Technology Review has an interesting article on gene therapy in the November/December, 2016 is (p.25) - Entitled "Gene Therapy Cure has Money-Back Guarantee."
FACTOR VIII GENE THERAPY NOVEMBER 2016
Convalescent Serum and Convalesent Plasma and Hyperimmune Globulins
Convalescent plasma is being used in the current Ebola crisis - the use of these products dates to 1918.
CONSIDERATIONS OF ADVANCES IN HEMOPHILIA THERAPEUTICS
BUS RIDING AND READING - Roast Pig, Lutefisk and hydroxycitrate
Some Interesting Articles on Gene Therapy
Ex vivo use of stem cells is moving quickly
Some MoreThoughts on Factor VIII Mimetics
Is there anything that truly substitute for factor VIII function?
Ion-Exchange Resins, Blood and Factor IX with a Note on Serum as Therapeutic
THROMBIN ADSORPTION TO FIBRIN
Some thoughts on the interaction of thrombin with fibrin including the affinity purification of thrombin in 1845.
PROTHROMBIN COMPLEX CONCENTRATES AND FACTOR VIIa
A recent article on thrombosis following use of prothrombin complex concentrates (Factor IX concentrates) and factor VIIa took me back to work in my laboratory in Chapel Hill some 40 years ago.
Arrowsmith, Clinical Trials, Compassionate Use and Phosphethanolamine
Sinclair Lewis has a message for today's scientific community
BLOODCURDLING MOVIES AND FACTOR VIII
Another interesting contribution to the lore of Factor VIII from Nemeth and coworkers in Leiden
Kidney organoids from stem cells
Future of organ tranplatation and a new platform for drug testing.
Gene-Editing takes Gene Therapy into Warp Drive
The future is now for gene therapy!
ANOTHER USE FOR FIBRIN SEALANT - FOOD PROCESSING
A description of the use of fibrin sealant in food processing.
Factor VIII in Interstitial Space
A discussion of the presence of factor VIII in the interstitial space and a possible role in fibrosis.
LUNG TRANSPLANTATION CURE VON WIILLEBRAND DISEASE
Some old observations and a Nature editorial
Why are some papers just missed?
HYALURONAN AND FIBRINOGEN - A UNIQUE COMBINATION
There is a unique interaction of hylauronan with fibrinogen that is likely of importance within the interstitial space,
A new (old) book on sulfhydryl chemistry
Jocelyn, P.C., Biochemistry of the SH Group, Academic Press, London, United Kingdom, 1972
CHO PROTEIN IN A THERAPETIC MAB
This is a very good article on the characterization of a protein impurity present in a monoclonal antibody therapeutic under development. It is an example how. despite my complaint of below,there is good science in biotechnology today.
CYSTEINE IN FACTOR VIII - 2015 UPDATE
CURRENT STATUS OF THE BIOMEDICAL RESEARCH ENTERPRISE (OR LACK THEREOF)
The Reaction of Ethylene Oxide with Biopharmaceuticals in Delivery Devices - Old Chemistry with new Analytical Technology
Gamma-thrombin for anticoagulant neutralization and thrombin for pain control - Thrombin goes to new places
Antibiotics from Soil - A Blast from the Past
Convalescent Serum is Passive Immunization in Ebola
Hazards in the Use of Synthetic Substrates for Recombinant Streptokinase
Some interesting material on the history of the development of antabus
Recent Developments in Therapeutics for Hemophilia A
Emphasis placed on the development of Factor VIII products with extended circulatory half-lives.
FACTOR VIII MIMICS IN THE TREATMENT OF HEMOPHILIA A-2013
A consideration of the development of mimics of factor VIII for use in the treatment of hemophilia A.
Ortholog Non-Equivalence in Matrix Metalloproteinase Function.
How far can you trust mouse data?
Thrombin versus Fibrin Sealant: Flathead versus Phillips
BIOMARKER DISCOVERY AND EVALUATION
Glandular Kallikrein in Saliva and Cancer
ORAL PROTEIN DRUG DELIVERY
Chemical Reagents for Protein Modification, 4th edition.
This is a major revision of the 3rd edition which was published in 2005. It is being published by CRC Press/Taylor and Francis).(http://www.crcpress.com)
Substitutes for Factor VIII in Hemophilia
A brief history of the development of mimeticss for Factor VIII which might have potential for therapeutic use.
Standard Operating Procedures and
Normalization of Deviance
A short comment on the importance of standard operating procedures for corporate survival. Adherence to standard operating proedures are critical to avoid normalization of deviance.
Evolution of Therapeutics for Hemophilia A
This is historical perspective on the development of therapeutics for hemophilia A. Most recent developments are posted above
An excellent book for those in the plasma biz.
Blood, Plasma and Plasma Proteins. A Unique Contribution to Modern Healthcare, ed. J.L. Valverde, IOS Press, Amsterdam, Netherlands, 2006
Cysteine Sulfenic Acid
Cysteine sulfenic acid is is of increasing interest and may be more common than expected. While revising Chemical Reagents for Protein Modification I have noticed a possible relationship to cystine oxides which may be of importance. I have also noticed that cysteine sulfenic acid can react with reagents such as N-ethylmaleimide.
IGIV and Infectious Disease -An under-apprecited application of an important biopharmaceutical product.
Serum is not Plasma is not Whole Blood
C1-Esterase Inhibitor -a serpin with multiple functions
Implants and Infection
I have recently celebrated the three month anniversary of my right knee athroplasty. Having time on my hands, I have gone back to topics from the past. One of these concerned the topical use of intravenous immunoglobulin and infection of implants. Fortunately I have avoided infection and am looking forward to spring practice where I might have an opportunity as a tackling dummy.
This post is being written on March 13, 2012 (Friday the 13tth comes on a Tuesday this month). The Ides of March are on the 15th and Saint Patrick's Day is this Saturday - thus green for the title. My recent total knee arthroplasty got me thinking about infecetious disease again and the potential of hyperimmune globulins - which encouraged me to assemble some thoughts on the matter. Given the issues of antibiotic resistance and emerging pathogens, passive immunization becomes an attractive consideration.
Salivary Kallikrein and Cancer
Many years ago I and colleagues observed that glandular kallikrein was elevated in saliva from patients with solid tumors distant from the oral cavity. This is still an observation looking for a explanation.
DETERMINATION OF PROTEIN CONCENTRATION
The days of concern about specific activity of proteins appears to vanished except for those involved in biopharmaceutical manufacture - here this analysis is an important part of product characterization. Sapan and Lundblad have a new contribution to methods for determination of protein concentration: Sapan, C.V. and Lundblad, R.L. (2015), Review of methods for determination of total protein concentration and peptide concentration in biological samples, Proteomics Clinical Applications 9, 268-276
Spring has come to the Research Triangle and the first pollen alert of the year was promulgated by the Weather Service today (February 28, 2012). I had lived in Chapel Hill for some 10 years before the infamous Chapel Hill pollen struck and has remained a blot on my existance ever since; going north to the Federation meetings in Atlantic City was a considerble relief. I have recently become award of allergoids and wish that some enterprising company interested in a project in practical immunotherapy would take note.
PLASMA PROTEINS IN THE EXTRAVASCULAR SPACE - I was surprised (modest understatment) on the amount of plasma protein outside of the vascular space. Fully 60% of albumin is outside of vascular space and the values for other plasma protein vary from 1% to 70%. While the rate of extravasation may depend on molecular size but this is not hard consideration. Some initial thoughts have been collected. Further material will appear in the future. At the moment the author is somewhat handicapped recovering from total knee replacement (result of a misspent youth and an oblate spheroid). This is an ongoing effort with new material being added on a sporadic basis. I was somewhat surprised (and embarrassed that I was surprised) to learn about the importance interstitial protein in transfusion medicine.
Plasma Proteinase Inhibitors This is taken from the end of a chapter from a book on biotechnology of plasma proteins
Serpins - More that Protease Inhibitors
Some speculations on antithrombin Some thougths on the requirements for high doses of antithrombin for acquired antithrombin deficiency
Some Thoughts on Innovation.
The group in the Department of Physical Chemistry at Harvard Medical School made many discoveries during their work on blood plasma fractionation during World War II. One of the somewhat overlooked projects was that of thrombin and fibrin foam. This product has seen a bit of renaissance but the illustreous background is somewhat ignored.
History of the delivery of thrombin to the gastrointestinal tract
A brief consideration of the history of plasma fractionation as well as some thoughts on the future.
Back to the Future or Play it Again Sam - some ruminations on how enzymology changes and remains the same.
Factor VIII Past Present and Future
Oral Protein Drug Delivery and Hemophilia A
In Vitro Assays for Therapeutic Enzymes There has been considerable interest in the use of enzyme kinetic analysis in the characterization of therapeutic enzymes. Some considerations are presented for discussion.
Factor VIII - Reducing Agents, Copper Ions, and Stability Some speculation on free sulfhydryl groups in factor VIII, copper ion and solution stability.
Use of Thrombin
for the Treatment of Esophageal Varices
Update on the
Therapeutic use of Thrombin