Chemistry Reference
In-Depth Information
more attention. Human
- defensins have antimicrobial, antiviral, cytokine - like
and antitoxic properties. Some of them also have lectin-like properties. We could
have recognized their carbohydrate-binding properties over two decades ago, had
we stopped to think about the curious behavior of HNP-1-3 when subjected to
size-exclusion chromatography on a Sephacryl S-200 column. Sephacryl is a trade-
name for a cross-linked copolymer of allyl dextran and
N
,
N
- methylenebisacryl-
amide, and dextran is a branched polysaccharide composed of glucose molecules.
HNP-1-3 eluted from our S200 column very late, with an elution volume consider-
ably larger than the column's bed volume. In contrast, HNP-4 eluted earlier, and
within the column's bed volume. In describing this behavior, we attributed the
delayed elution of HNP- 1 - 3 to ' nonspecifi c interactions between these peptides
and the gels matrix'. Neoglycoproteins as tools (please see Chapter 4.3) document
HD-5's capacity to home in on carbohydrates in multivalent interactions [10] .
Among the human
α
- defensins, only HNP - 1 - 3 and HD -5 are lectins. Info Box 2
lists fi ve reasons why an ability to bind carbohydrates could be useful for
α
α
- defen-
sins. The other human
- defensins, HNP -4 and HD-6, had little or no affi nity for
carbohydrates in our studies.
Although HBDs 1-3 did not exhibit carbohydrate-binding properties in our
studies, they represent fewer than 10% of all the
α
β
- defensins in the human
genome. In rodents, many
-defensins are expressed in the male reproductive
tract, especially in the epididymis. Alternative splicing has enabled one rat epididy-
mal
β
-defensin, called 'E3', to acquire a lectin domain that resembles one found
in wheat germ agglutinin [11]. Rat spermatozoa are coated with this hybrid lectin-
β
Info Box 2
Five possible reasons why HNP - 1 - 3 bind carbohydrates are:
(i)
Since they are stored in azurophil granules that have a peptidoglycan-rich
matrix, electrostatic and lectin-like interactions with this matrix may
prevent their premature release.
(ii)
The affi nity of secreted HNP- 1 - 3 for cell - surface glycoproteins and glyco-
lipids should concentrate these peptides at a cell's surface, positioning
them optimally to intercept incoming bacteria, viruses or toxins.
(iii) HNP - 1 - 3 is chemotactic for monocytes, immature dendritic cells and
certain T cells. The gradual elution of defensins from cell surface glyco-
molecules can establish a longer lasting chemotactic gradient.
(iv) The small size of defensins makes them subject to rapid clearance by renal
glomerular fi ltration, unless they bind larger serum glycoproteins.
(v) Immunoglobulins (IgG, IgM and IgA) are glycoproteins that bind
HNP - 1 - 3 reversibly and with high affi nity (unpublished). Perhaps defen-
sin-carrying immunoglobulins are a natural embodiment of Ehrlich's
century - old ' magic bullet ' concept.
